Life Glow Plus Super Life Glow Life Glow Basic Bone Dense Calcium Taheebo Life Tea Germanium Colloidal Minerals Methyl Sulfonyl Methane Transfer Factor Immune Egg	Vibrant Life Home Web All VL Products Family Of Three Chelation Formulas Oral Chelation Ingredient Comparisons The Wednesday Letter Karl Loren Viewpoints Frequently Asked Questions Testimonials Free Radicals Central Page For 18 Web Sites	Vibrant Life Home Page Shopping Cart	Separate Search Page or search below Loading
Navigation Help	Karl Loren Background	Ingredients Technical	Write To Karl Loren	Table Of Contents

Ornithine Technical Reports

Ornithine is an amino acid that works to prevent cancer and improve the immune system.  Here are a group of medical studies which describe this role for Ornithine.

Here are a few definitions that may help:

Top

HealthGate Documents

Record 1 from database: MEDLINE
Return To The Top

Title

Transport of thyroid hormones to target tissues.

Author

Ekins RP; Sinha AK; Pickard MR; Evans IM; al Yatama F

Address

Division of Molecular Endocrinology, University College London Medical School, United Kingdom.

Source

Acta Med Austriaca, 1994, 21:2, 26-34

Abstract

Endemic iodine deficiency is associated with maternal hypothyroxinemia and a relatively high incidence of neurological disorders in the offspring. The previous assumption that the placenta is impermeable to maternal thyroid hormone, has resulted in the erroneous suggestion that iodine per se has an essential role in brain development. Furthermore, the observed factorial rise in thyroxine-binding globulin (TBG) in pregnancy has often been misinterpreted as preventing thyroid hormone loss to either the fetal compartment or excretory systems. However, physiochemical analysis of the role of specific binding proteins in hormone delivery, combined with epidemiological evidence and evolutionary considerations has led us to postulate that a) maternal thyroxine (T4) is transported to the fetus, and is of crucial importance in early fetal development, and b) TBG forms part of a control system specifically designed to maintain at an optimal level the T4 environment to which the developing fetus is exposed. Placental transfer of maternal T4 in a variety of mammalian species (including humans) is now well established. Further experimental studies in rats have shown that perturbation of the intrauterine thyroid hormone environment during critical phases of brain development results in a spectrum of biochemical dysgenesis. For example, in fetal brains deriving from hypothyroxinemic (Tx) rat dams, severe disruption of phosphate metabolism is observed and the ontogenesis of two enzyme activities associated with growth control, protein kinase C and ornithine decarboxylase, are compromised. Development of brain function is also impaired, as evidenced by the dysgenesis of certain neurotransmitter metabolic activities (choline acetyltransferase and DOPA decarboxylase).(ABSTRACT TRUNCATED AT 250 WORDS)

Language of Publication

English

Unique Identifier

95091118

MeSH Heading (Major)

Fetal Development|*PH; Goiter, Endemic|*PP; Maternal-Fetal Exchange|*PH; Thyroid Hormones|*BL

MeSH Heading

Animal; Brain|EM; Carrier Proteins|PH; Female; Fetal Organ Maturity|PH; Human; Infant, Newborn; Membrane Proteins|PH; Pregnancy; Rats; Support, Non-U.S. Gov't; Thyroid Gland|EM; Thyroxine|BL; Thyroxine-Binding Proteins|PH

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0303-8173

Country of Publication

AUSTRIA

Record 2 from database: MEDLINE
Return To The Top

Title

Biochemical and growth-modulatory effects of the new S-adenosylmethionine decarboxylase inhibitor CGP 48664 in malignant and immortalized normal human breast epithelial cells in culture.

Author

Manni A; Badger B; Wechter R; Kunselman S; Rossini A; Demers L

Address

Department of Medicine, Pennsylvania State University College of Medicine, Hershey 17033, USA.

Source

Int J Cancer, 1995 Aug, 62:4, 485-91

Abstract

CGP 48664 [4-aminoindanon-1-(2'-amidino)hydrazone dihydrochloride monohydrate] is a newly introduced inhibitor of S-adenosylmethionine decarboxylase (SAMDC) with increased selectivity of action and reduced toxicity. We analyzed the biochemical and antiproliferative effects of this compound in a panel of hormone-dependent (3 clones of MCF-7, T47D) and -independent (MDA-MB-231, BT-20) human breast cancer cell lines in culture. For comparison, we also tested its effects in the spontaneously immortalized human breast epithelial cell line MCF-10A. All cell lines were highly sensitive to the growth-inhibitor effect of CGP 48664 with an IC50 between 0.1 and 0.5 microM. A dose-dependent bell-shaped increase in SAMDC was observed in normal and malignant breast cells resulting from enzyme stabilization by the inhibitor as supported by Western blot analysis. While ornithine decarboxylase (ODC) activity consistently increased, the effect of CGP 48664 on spermidine/spermine N'acetyltransferase (SSAT) was variable in the breast cancer cell lines. In contrast, the inhibitor consistently reduced SSAT activity level in the MCF-10A cell line and its derivative partially transformed by a mutated ras oncogene. As expected cellular putrescine levels were markedly increased by CGP 48664 administration, whereas spermidine and spermine contents were reduced. However, the degree of reduction was usually only moderate. Furthermore, exogenous polyamine administration was relatively ineffective in rescuing the antiproliferative effect of CGP 48664 in MCF-7 cells, while exerting a more complete rescue in the MDA-MB-231 cell line. We conclude that CGP 48664 exerts a potent growth-inhibitory effect on mammary cells in culture. However, its action may not always be entirely mediated through the polyamine pathway.

Language of Publication

English

Unique Identifier

95362369

MeSH Heading (Major)

Acetyltransferases|*ME; Adenosylmethionine Decarboxylase|*AI; Amidines|*PD; Breast|*DE/EN/PA; Breast Neoplasms|*DT/EN/PA; Indans|*PD; Ornithine Decarboxylase|*ME

MeSH Heading

Cell Division|DE; Cell Line, Transformed; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Human; Neoplasms, Hormone-Dependent|DT; Spermidine|ME/PD; Spermine|PD; Support, U.S. Gov't, P.H.S.; Tumor Cells, Cultured

Publication Type

JOURNAL ARTICLE

ISSN

0020-7136

Country of Publication

UNITED STATES

Record 3 from database: MEDLINE
Return To The Top

Title

Structure-activity relations of S-adenosylmethionine decarboxylase inhibitors on the growth of MCF-7 breast cancer cells.

Author

Thomas T; Faaland CA; Adhikarakunnathu S; Thomas TJ

Address

Department of Environmental & Community Medicine, Environmental and Occupational Health Sciences Institute, New Brunswick, NJ, USA.

Source

Breast Cancer Res Treat, 1996, 39:3, 293-306

Abstract

SAMDC is a key enzyme in the biosynthesis of spermidine and spermine, 2 polyamines that are essential for cell proliferation. Inhibition of polyamine biosynthesis is often targeted as a therapeutic strategy to suppress cancer cell growth as these cells contain elevated levels of polyamines. We examined the effect of a new group of SAMDC inhibitors, CGP33829, CGP35753, CGP36958, CGP39937, and CGP48664, (obtained from Ciba-Geigy, Basel, Switzerland), and their parent compound, MGBG, on the proliferation of MCF-7 breast cancer cells. MGBG had minimal effects on the proliferation of MCF-7 cells up to 6 microM concentration. In contrast, CGP48664 and CGP39937, containing 2 aromatic rings that delocalize the pi electron system of the backbone of MGBG, were potent inhibitors with 50% growth inhibition at 0.5 microM concentration. Other CGP compounds were less effective in inhibiting cell growth. The ability of CGP48664 to inhibit MCF-7 cell proliferation was related to its ability to inhibit SAMDC and to consequently deplete spermidine and spermine levels in the cell. Exogenous spermidine and spermine could reverse the growth inhibitory effects of this compound. CGP compounds also increased the activity of ODC, another enzyme involved in polyamine biosynthesis. Northern blot analysis of mRNA from MCF-7 cells progressing in cell cycle after G1 synchronization did not show an increase in ODC mRNA level by CGP48664. These data demonstrate structure-activity relationships of a series of MGBG derivatives on cell growth, enzyme activities, and polyamine biosynthesis in a hormone-responsive breast cancer cell line and suggest potential application of SAMDC inhibitors as therapeutic agents.

Language of Publication

English

Unique Identifier

97031083

MeSH Heading (Major)

Adenosylmethionine Decarboxylase|*AI/GE; Antineoplastic Agents|*PD; Breast Neoplasms|*DT/PA; Enzyme Inhibitors|*PD

MeSH Heading

Acetyltransferases|ME; Amidines|PD; Biogenic Polyamines|AN; Cell Division|DE; Estradiol|PD; Female; Human; Indans|PD; Mitoguazone|PD; Ornithine Decarboxylase|ME; RNA, Messenger|AN; Structure-Activity Relationship; Support, U.S. Gov't, P.H.S.; Tumor Cells, Cultured

Publication Type

JOURNAL ARTICLE

ISSN

0167-6806

Country of Publication

NETHERLANDS

Record 4 from database: MEDLINE
Return To The Top

Title

Polyamine profiles and growth properties of ornithine decarboxylase overexpressing MCF-7 breast cancer cells in culture.

Author

Manni A; Wechter R; Grove R; Wei L; Martel J; Demers L

Address

Department of Medicine, Pennsylvania State University College of Medicine, Hershey 17033, USA.

Source

Breast Cancer Res Treat, 1995 Apr, 34:1, 45-53

Abstract

To determine the direct influence of the polyamine (PA) pathway on breast cancer phenotype, we employed a transfection approach to induce overexpression of the PA biosynthetic enzyme ornithine decarboxylase (ODC) in the hormone-responsive MCF-7 breast cancer cell line. Using a modified calcium phosphate method and an ODC cDNA coding for a truncated and more stable enzyme, we were able to achieve a moderate to marked degree of ODC overexpression (up to 150-fold) in a transient transfection system. ODC-overexpressing MCF-7 cells exhibited a selective increase in cellular putrescine content, while the levels of spermidine and spermine remained unaffected. Under defined culture conditions, overexpression of ODC resulted in a consistent but modest increase in [3H]thymidine incorporation into DNA which was similar in the presence and absence of 17-beta-estradiol, TGF-alpha, and IGF-I. In the presence of serum, the effect of ODC overexpression on basal [3H]-thymidine incorporation into DNA was inconsistent, possibly as a result of subtle differences in culture conditions. Overall, our results support the hypothesis that activation of the PA biosynthetic pathway may confer a growth advantage to breast cancer cells.

Language of Publication

English

Unique Identifier

95268110

MeSH Heading (Major)

Breast Neoplasms|*EN/GE/PA; Ornithine Decarboxylase|GE/*ME

MeSH Heading

Cell Division; Female; Gene Expression Regulation, Enzymologic; Human; Polyamines|ME; Support, U.S. Gov't, P.H.S.; Transfection; Tumor Cells, Cultured

Publication Type

JOURNAL ARTICLE

ISSN

0167-6806

Country of Publication

NETHERLANDS

Record 5 from database: MEDLINE
Return To The Top

Title

Prevention of breast cancer in premenopausal women.

Author

Love RR

Address

University of Wisconsin Comprehensive Cancer Center, Department of Human Oncology, Madison 53706.

Source

J Natl Cancer Inst Monogr, 1994, :16, 61-5

Abstract

While all-inclusive complete models for breast cancer development are not available, four concepts are likely to be critical to creation of well-grounded breast cancer prevention efforts: 1) step-by-step progressive development, 2) involving multiple factors, 3) over several years, and 4) during a long period of which the process may be reversible. Interventions to prevent breast cancer must have a comprehensive biological rationale, an absence of serious toxic effects, and long-term acceptability by women. Prophylactic mastectomy may be beneficial in some women, but identification of individuals at very high risk for breast cancer remains elusive. At present, greater attention to four manipulable risk factors is appropriate: radiation, smoking, alcohol, and lactation. Clinical trials are in the process of studying a synthetic retinoid (4-hydroxyphenylretinamide), tamoxifen, and a low-fat diet. Other breast cancer prevention strategies in various phases of preclinical trial evaluation include: pseudopregnancy, an "ideal" combination oral contraceptive, luteinizing hormone-releasing hormone (LHRH) agonist oophorectomy, modification of estrogen metabolism, suppression of ornithine decarboxylase induction, and manipulation of growth factors.

Language of Publication

English

Unique Identifier

95092435

MeSH Heading (Major)

Breast Neoplasms|EP/ET/*PC

MeSH Heading

Adult; Ataxia Telangiectasia|CO; Cocarcinogenesis; Contraceptives, Oral, Hormonal|AE/TU; Dietary Fats|AD/AE; Estrogens|ME; Female; Fenretinide|PD; Gonadorelin|AG; Human; Lactation; Mastectomy; Neoplasms, Radiation-Induced|PC; Ornithine Decarboxylase|AI; Premenopause; Prospective Studies; Pseudopregnancy|CI; Randomized Controlled Trials; Risk Factors; Smoking; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tamoxifen|TU; Temperance; Time Factors

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

1052-6773

Country of Publication

UNITED STATES

Record 6 from database: MEDLINE
Return To The Top

Title

Antiproliferative effect of curcumin (diferuloylmethane) against human breast tumor cell lines.

Author

Mehta K; Pantazis P; McQueen T; Aggarwal BB

Address

Department of Bioimmunotherapy, The University of Texas MD Anderson Cancer Center, Houston 77030, USA.

Source

Anticancer Drugs, 1997 Jun, 8:5, 470-81

Abstract

Pharmacologically safe compounds that can inhibit the proliferation of tumor cells have potential as anticancer agents. Curcumin, a diferuloylmethane, is a major active component of the food flavor turmeric (Curcuma longa) that exhibits anticarcinogenic properties in vivo. In vitro, it suppressed c-jun/Ap-1 and NF-kappaB activation and type 1 human immunodeficiency virus long-terminal repeat-directed gene expression. We examined the antiproliferative effects of curcumin against several breast tumor cell lines, including hormone-dependent and -independent and multidrug-resistant (MDR) lines. Cell growth inhibition was monitored by [3H]thymidine incorporation, Trypan blue exclusion, crystal violet dye uptake and flow cytometry. All the cell lines tested, including the MDR-positive ones, were highly sensitive to curcumin. The growth inhibitory effect of curcumin was time- and dose-dependent, and correlated with its inhibition of ornithine decarboxylase activity. Curcumin preferentially arrested cells in the G2/S phase of the cell cycle. Curcumin-induced cell death was neither due to apoptosis nor to any significant change in the expression of apoptosis-related genes, including Bcl-2, p53, cyclin B and transglutaminase. Overall our results suggest that curcumin is a potent antiproliferative agent for breast tumor cells and may have potential as an anticancer agent.

Language of Publication

English

Unique Identifier

97358515

MeSH Heading (Major)

Antineoplastic Agents|*PD; Breast Neoplasms|*PA; Curcumin|*PD

MeSH Heading

Antibiotics, Anthracycline|PD; Blotting, Western; Cell Cycle|DE; Cell Division|DE; Cell Line; Doxorubicin|PD; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Human; Ornithine Decarboxylase|ME; Support, Non-U.S. Gov't; Tetrazolium Salts; Thiazoles

Publication Type

JOURNAL ARTICLE

ISSN

0959-4973

Country of Publication

ENGLAND

Record 7 from database: MEDLINE
Return To The Top

Title

Can arginine and ornithine support gut functions?

Author

Cynober L

Address

Laboratoire de Biochimie, HÈopital Saint-Antoine, Paris, France.

Source

Gut, 1994 Jan, 35:1 Suppl, S42-5

Abstract

Arginine and ornithine are precursors of nitric oxide and polyamines, respectively. These metabolites intimately participate in permeability and adaptive responses of the gut. The liver possesses high arginase activity as an intrinsic part of urea synthesis and would consume most of the portal supply of dietary arginine. The gut reduces this possibility by converting dietary arginine to citrulline, which effectively bypass the liver and is resynthesized to arginine in the kidney. Dietary ornithine supplementation, in the form of ornithine alpha-ketoglutarate (OKG) can be considered as an arginine precursor. Several supplement studies have shown both amino acids to promote growth hormone and insulin secretion with anabolic effects in postoperative patients. Their intermediary metabolites (for example, glutamine, proline) may also be of benefit in trauma metabolism. Specific effects of either amino acid on the gut are poorly reported. One recent animal study showed improved morphology after OKG administration, perhaps through increased polyamine secretion. Generation of nitric oxide from arginine has two facets. Excess production from high dose arginine potentiated the effects of experimentally induced sepsis, whereas low doses improved survival. These considerations suggest that the role of enteral diet supplementation with arginine or OKG should be urgently examined for any benefits it may have on mucosal barrier function.

Language of Publication

English

Unique Identifier

94171129

MeSH Heading (Major)

Arginine|*ME/PD; Enteral Nutrition|*; Intestines|DE/ME/*PH; Ornithine|*ME/PD

MeSH Heading

Citrulline|ME; Human; Nitric Oxide|ME

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0017-5749

Country of Publication

ENGLAND

Record 8 from database: MEDLINE
Return To The Top

Title

Chlorpheniramine inhibits the synthesis of ornithine decarboxylase and the proliferation of human breast cancer cell lines [published erratum appears in Breast Cancer Res Treat 1996;37(1):97]

Author

Medina MA; García de Veas R; Morata P; Lozano J; Sánchez Jiménez F

Address

Laboratorio de BioquÆimica y BiologÆia Molecular, Facultad de Ciencias, Universidad de MÆalaga, Spain.

Source

Breast Cancer Res Treat, 1995 Aug, 35:2, 187-94

Abstract

Proliferation of both mouse and human breast cancer cells was inhibited by chlorpheniramine (CPA) in a dose-response manner. At the beginning of the exponential phase of growth (two days after seeding), 250 microM CPA was able to reduce cell proliferation by 75% (in Ehrlich cell cultures) and 30% (in MCF-7 cultures). The antiproliferative effect of CPA was also tested on a poorly-differentiated and hormone-insensitive human breast cancer cell line (MDA-MB231) and on a highly proliferative human colon cancer cell line (clone 3). CPA was cytotoxic for MDA-MB231 cells at concentrations higher than 50 microM, and it was also cytotoxic for the colon cancer cell clone 3 at 250 microM CPA. Nevertheless, colon cancer cells were slightly stimulated at CPA concentrations less than 100 microM. CPA reduced (by 50-70%) the ornithine decarboxylase induction occurring early after culture seeding of experimental mammary tumors (Ehrlich carcinoma cells) and human breast cancer cells (MCF-7). The presented data suggest that in addition to ODC inhibition, CPA presents other still unknown cytotoxic effects.

Language of Publication

English

Unique Identifier

95375276

MeSH Heading (Major)

Breast Neoplasms|*EN/PA; Chlorpheniramine|*PD; Ornithine Decarboxylase|*BI/GE

MeSH Heading

Animal; Cell Division|DE; Colonic Neoplasms|EN/GE/PA; Dose-Response Relationship, Drug; Gene Expression Regulation, Enzymologic|DE; Human; Mammary Neoplasms, Experimental|EN/GE/PA; Mice; RNA, Messenger|GE; Support, Non-U.S. Gov't; Tumor Cells, Cultured

Publication Type

JOURNAL ARTICLE

ISSN

0167-6806

Country of Publication

NETHERLANDS

Record 9 from database: MEDLINE
Return To The Top

Title

Intrinsic and extrinsic factors in estrogen action in human breast cancer: role of polyamines and pituitary factors.

Author

Shiu RP; Lima G; Leung CK; Dembinski TC

Address

 

Source

J Steroid Biochem, 1986 Jan, 24:1, 133-8

Abstract

Although polyamines are important in regulating proliferation of mammalian cells, their role in hormone induction of cell growth has not been delineated. In the estradiol-responsive human breast cancer cell line, T-47D clone 11, estradiol (10(-10) M) was able to stimulate cell proliferation and the activity of

decarboxylase (ODC), the first and rate-limiting enzyme in the biosynthesis of polyamines. alpha-Difluoromethylornithine (DFMO), a specific inhibitor of ODC, blocked the estradiol-induced cell proliferation and ODC activity. Exogenous addition of putrescine, the natural product of ODC, rescued the inhibitory effect of DFMO. In addition, DFMO abolished the estradiol-induced growth of several other estrogen-responsive human breast cancer cell lines but did not affect the growth of hormone-independent cell lines. Further, a serum factor was found to be required for estradiol to exert its effect. To gain insight into the nature of this and possibly other extrinsic factors involved, the effect of estradiol on the proliferation of T-47D cells transplanted into athymic nude mouse was evaluated. In this in vivo system, estradiol alone produced only moderate growth of the human breast tumor. The simultaneous transplantation of a prolactin (PRL)- and growth hormone (GH)-secreting rat pituitary tumor or normal rat pituitary glands at a different site dramatically potentiated the effect of estradiol on the growth of the breast tumor xenograft. Purified PRL or GH were without effect, indicating that the active pituitary factor is neither PRL nor GH. Further, conditioned medium from rat pituitary tumor cells potentiated the mitogenic effect of estradiol on T-47D and several other estrogen receptor-positive human breast cancer cell lines in vitro under serum-free condition. In conclusion, we have identified both intrinsic (polyamines) and extrinsic (pituitary/serum) factors that are importance for estrogen to exert its mitogenic action. The next goal will be to elucidate the mechanisms of action of these molecules in the modulation of estrogen action.

Language of Publication

English

Unique Identifier

86201682

MeSH Heading (Major)

Breast Neoplasms|*PA; Estrogens|*PD; Pituitary Gland|*PH; Polyamines|*ME

MeSH Heading

Animal; Cell Line; Drug Synergism; Female; Human; Mice; Mice, Nude; Neoplasm Transplantation; Ornithine|AA/PD; Ornithine Decarboxylase|AN; Pituitary Neoplasms|SE; Support, Non-U.S. Gov't; Transplantation, Heterologous

Publication Type

JOURNAL ARTICLE

ISSN

0022-4731

Country of Publication

ENGLAND

CAS Registry/EC Number

EC 4.1.1.17 (Ornithine Decarboxylase); 0 (Estrogens); 0 (Polyamines); 70052-12-9 (Eflornithine); 7006-33-9 (Ornithine)

Record 10 from database: MEDLINE
Return To The Top

Title

Ornithine alpha-ketoglutarate in nutritional support.

Author

Cynober L

Address

Laboratoire de Biochimie, Hopital Saint Antoine, Paris, France.

Source

Nutrition, 1991 Sep-Oct, 7:5, 313-22

Abstract

Ornithine alpha-ketoglutarate (OKG) is a salt formed of two molecules of ornithine and one molecule of alpha-ketoglutarate. OKG has been successfully used by the enteral and parenteral route in burn, traumatized, and surgical patients and in chronically malnourished subjects. According to the metabolic situation, OKG treatment decreases muscle protein catabolism and/or increases synthesis. In addition, OKG promotes wound healing. The mechanism of action of OKG is not fully understood, but the secretion of anabolic hormones (insulin, human growth hormone) and the synthesis of metabolites (glutamine, polyamines, arginine, ketoacids) may be involved.

Language of Publication

English

Unique Identifier

92208515

MeSH Heading (Major)

Nutrition|*; Ornithine|*AA/AD/AE/CH/ME/PK/TU

MeSH Heading

Animal; Chemistry, Physical; Enteral Nutrition; Human; Nutrition Disorders|TH; Parenteral Nutrition; Wound Healing

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0899-9007

Country of Publication

UNITED STATES

CAS Registry/EC Number

37339-58-5 (ornicetil); 7006-33-9 (Ornithine)

Record 11 from database: MEDLINE
Return To The Top

Title

Role of ornithine decarboxylase in proliferation of prolactin-dependent lymphoma cells.

Author

Elsholtz HP; Shiu RP; Friesen HG

Address

 

Source

Biochem Cell Biol, 1986 May, 64:5, 381-6

Abstract

Mitogenic stimulation of Nb2 lymphoma cells by lactogenic hormones (prolactin, human growth hormone) caused a dramatic early increase in ornithine decarboxylase (ODC) activity that achieved a maximal level by 6-8 h. A marked increase in ODC activity was also generated when cells which had reached a growth plateau were transferred to fresh medium that did not stimulate growth. Furthermore, low concentrations of human growth hormone (20 pg/mL) elicited a proliferative response, but did not cause a detectable early increase in ODC activity. The early peak of ODC activity thus appeared not to be directly involved in mediating lactogen-stimulated growth nor was it required to support the mitogenic response. However, prolonged suppression of ODC activity by DL-alpha-difluoromethylornithine (DFMO) (200 microM) attenuated the growth of Nb2 cells (50-60% inhibition), indicating that normal cell growth was dependent on ODC and polyamine biosynthesis. Under these conditions, putrescine, the enzyme product, or the polyamines spermidine and spermine restored normal cell growth when added at a concentration of 1 microM or greater. Nb2-SP cells, variants which proliferate in the absence of prolactin, were about two times more resistant to the growth suppressive effects of DFMO than prolactin-responsive Nb2 cells.

Language of Publication

English

Unique Identifier

86242765

MeSH Heading (Major)

Lymphoma|EN/*PA; Ornithine Decarboxylase|AI/*ME; Prolactin|*PD; Somatotropin|*PD

MeSH Heading

Animal; Cell Division|DE; Cell Line; Human; Kinetics; Ornithine|AA/PD; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE

ISSN

0829-8211

Country of Publication

CANADA

CAS Registry/EC Number

EC 4.1.1.17 (Ornithine Decarboxylase); 70052-12-9 (Eflornithine); 7006-33-9 (Ornithine); 9002-62-4 (Prolactin); 9002-72-6 (Somatotropin)

Record 12 from database: MEDLINE
Return To The Top

Title

Synthesis and biological evaluation of superactive agonists of growth hormone-releasing hormone.

Author

Izdebski J; Pinski J; Horvath JE; Halmos G; Groot K; Schally AV

Address

Department of Medicine, Tulane University School of Medicine, New Orleans, LA 70146, USA.

Source

Proc Natl Acad Sci U S A, 1995 May, 92:11, 4872-6

Abstract

Analogs of the 29 amino acid sequence of human growth hormone-releasing hormone (hGH-RH) with agmatine (Agm) in position 29, desaminotyrosine (Dat) in position 1, norleucine (Nle) in position 27, and L-alpha-aminobutyric acid (Abu) in position 15 have been synthesized, and their biological activity was evaluated. Some peptides contained one or two residues of ornithine (Orn) instead of Lys in positions 12 and 21 and additional replacements in positions 8 and 28. All analogs were found to be more potent than hGH-RH-(1-29)-NH2 in the superfused rat pituitary cell system. In tests in vivo in rats after subcutaneous administration, the analogs JI-22, [Dat1, Orn12,21, Abu15, Nle27, Agm29]hGH-RH-(1-29); JI-34, [Dat1, Orn12,21,Abu15,Nle27, Asp28, Agm29]hGH-RH-(1-29); JI-36, [Dat1, Thr8, Orn12,21, Abu15,Nle27,Asp28,Agm29]hGH-RH-(1-29); and JI-38, [Dat1,Gln8, Orn12,21,Abu15,Nle27,Asp28,Agm29]hGH-RH-(1 -29) displayed a potency 44.6,80.9,95.8, and 71.4 times greater, respectively, than that of hGH-RH-(1-29)-NH2 at 15 min and 217.1, 89.7, 87.9, and 116.8 times greater at 30 min. After intravenous administration, JI-22, JI-36, and JI-38 were 3.2-3.8 times more potent than hGH-RH-(1-29)-NH2 at 5 min and 6.1-8.5 times more active at 15 min. All analogs were found to have higher binding affinities for GH-RH receptors on rat pituitary cells than hGH-RH-(1-29)-NH2. Because of high activity and greater stability, these analogs could be considered for therapy of patients with growth hormone deficiency.

Language of Publication

English

Unique Identifier

95281558

MeSH Heading (Major)

Oligopeptides|CS/*PD; Pituitary Gland|DE/*SE; Somatotropin|BL/*SE; Somatotropin-Releasing Hormone|*AA/AG/*CS/PD

MeSH Heading

Amino Acid Sequence; Animal; Comparative Study; Human; In Vitro; Male; Molecular Sequence Data; Rats; Rats, Sprague-Dawley; Receptors, Neuropeptide|ME; Receptors, Pituitary Hormone-Regulating Hormone|ME; Structure-Activity Relationship; Support, U.S. Gov't, Non-P.H.S.

Publication Type

JOURNAL ARTICLE

ISSN

0027-8424

Country of Publication

UNITED STATES

Record 13 from database: MEDLINE
Return To The Top

Title

Effects of parathyroid hormone-related peptide on adenosine 3',5'-monophosphate and ornithine decarboxylase in a human colonic cell line.

Author

Yu D; Seitz PK; Selvanayagam P; Rajaraman S; Townsend CM Jr; Cooper CW

Address

Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77550.

Source

Endocrinology, 1992 Apr, 130:4, 1993-2000

Abstract

PTH-related peptide (PTHrP) is widely distributed in normal tissues, including the gut, and is considered a potential autocrine or paracrine regulator of cellular growth and differentiation. With this in mind, a human colonic cell line (LoVo) was used to study the effect of PTHrP on ornithine decarboxylase (ODC), because ODC is known to have profound effects on the growth and differentiation of many cell types via stimulation of synthesis of polyamines. cAMP also was measured, because this second messenger has been implicated in the regulation of ODC activity. Nearly confluent LoVo cells, grown in F-12 medium and 10% fetal bovine serum (FBS), were preincubated in 1% FBS for at least 5 h, and then PTHrP-(1-34) was added, and the incubation was continued for up to 6 h. Cell extracts were analyzed for ODC activity by measuring 14CO2 liberated from 14C-labeled ornithine, for cAMP by RIA, and for ODC mRNA by Northern analysis. PTHrP produced dose-related increases in both cAMP (2- to 3-fold) and ODC (3- to 5-fold), with a maximal effect at 0.1-1 microM and an ED50 of 1-10 nM. Comparison of the cAMP and ODC responses to PTHrP showed a strong correlation (r = 0.96; P less than 0.001). The effects of 1 microM PTHrP-(1-34) to increase cAMP and ODC were completely inhibited by 10-20 microM of the specific antagonist [Asn10,Leu11]PTHrP-(7-34). PTHrP-(1-34) did not stimulate ODC activity when cells were incubated without FBS. The stimulation of ODC activity by PTHrP-(1-34) was maximal at 2 h, a time at which an increase in ODC mRNA also was evident. PTH-(1-34) and forskolin also stimulated ODC activity, but PTHrP-(67-86) amide was ineffective. The results indicate that the N-terminal portion of the PTHrP molecule can stimulate ODC activity in a human colon cell line and that the effect is probably mediated by cAMP. The results are consistent with the idea that PTHrP may influence cell growth and differentiation in the gut via an effect on polyamine biosynthesis. Since LoVo cells also express PTHrP mRNA, this gastrointestinal cell line may serve as a useful model for studying autocrine regulation of gut cell growth and differentiation by PTHrP.

Language of Publication

English

Unique Identifier

92191895

MeSH Heading (Major)

Colon|CH/*DE; Cyclic AMP|*AN; Ornithine Decarboxylase|*AN/GE; Parathyroid Hormones|*PD; Proteins|GE/*PD

MeSH Heading

Cell Line; Human; Peptide Fragments|PD; RNA, Messenger|AN; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE

ISSN

0013-7227

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 4.1.1.17 (Ornithine Decarboxylase); 0 (parathyroid hormone-related protein); 0 (Parathyroid Hormones); 0 (Peptide Fragments); 0 (Proteins); 0 (RNA, Messenger); 112540-82-6 (hypercalcemic hormone of malignancy (1-34)); 52232-67-4 (Teriparatide); 60-92-4 (Cyclic AMP)

Record 14 from database: MEDLINE
Return To The Top

Title

Effects of vasoactive intestinal peptide on adenosine 3',5'-monophosphate, ornithine decarboxylase, and cell growth in a human colon cell line.

Author

Yu D; Seitz PK; Selvanayagam P; Rajaraman S; Townsend CM Jr; Cooper CW

Address

Department of Pharmacology, University of Texas Medical Branch, Galveston 77550.

Source

Endocrinology, 1992 Sep, 131:3, 1188-94

Abstract

Vasoactive intestinal peptide (VIP) is a widely distributed neuropeptide that has been considered a potential regulator of cell growth and differentiation in various tissues, including the gut. To examine this idea, we used a human colon carcinoma cell line (LoVo) as a model system and measured ornithine decarboxylase (ODC), because this is the rate-limiting enzyme for the formation of polyamines, which are thought to be key factors in regulating cell growth. LoVo cells, grown to about 80% confluence in F-12 medium containing 10% fetal bovine serum, were preincubated for 5 h in low serum medium (1% fetal bovine serum in F-12), and ODC activity was determined by measuring 14CO2 liberated from 14C-labeled ornithine. VIP caused a dose-related biphasic change in ODC, with activity increased at 10 pM, maximal (5-fold increase) at 10 nM, and decreased toward basal at 100 nM to 1 microM. Incubation of cells for 6 days with VIP in low serum medium showed similar changes in cell numbers, with growth being increased by doses in the 1 pM to 100 nM range and decreased at higher doses (greater than or equal to 100 nM). Exposure of cells to 5 mM alpha-difluoromethylornithine blocked both the VIP-induced increase in cell number and the VIP-induced increase in ODC activity. Increased ODC mRNA was detected after 2 h of exposure to VIP, a time at which ODC activity peaked after treatment, and the increase in ODC mRNA caused by VIP was dose-dependent. In related experiments LoVo cells were found to have high affinity VIP receptors (Kd = 0.4 nM), as assessed by examination of [125I]VIP binding in the presence of varying concentrations of unlabeled VIP. Studies of intracellular cAMP revealed a dose-related increase in cAMP in response to VIP (ED50 = 11 pM), and the adenylate cyclase activator forskolin increased both ODC activity and ODC mRNA. The findings support the idea that LoVo cells have VIP receptors linked to cAMP which can stimulate cell growth at least in part by increasing ODC synthesis and activity, thereby altering the production of polyamines. The decreased growth and ODC activity observed with high doses of VIP may involve a second messenger other than cAMP.

Language of Publication

English

Unique Identifier

92371314

MeSH Heading (Major)

Cell Division|*DE; Cyclic AMP|*ME; Ornithine Decarboxylase|GE/*ME; Vasoactive Intestinal Peptide|ME/*PD

MeSH Heading

Adenocarcinoma; Blotting, Northern; Cell Line; Colonic Neoplasms; Dose-Response Relationship, Drug; Eflornithine|PD; Human; Kinetics; Receptors, Gastrointestinal Hormone|ME; RNA, Messenger|ME; RNA, Neoplasm|GE/IP; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE

ISSN

0013-7227

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 4.1.1.17 (Ornithine Decarboxylase); 0 (Receptors, Gastrointestinal Hormone); 0 (Receptors, Vasoactive Intestinal Peptide); 0 (RNA, Messenger); 0 (RNA, Neoplasm); 37221-79-7 (Vasoactive Intestinal Peptide); 60-92-4 (Cyclic AMP); 70052-12-9 (Eflornithine)

Record 15 from database: MEDLINE
Return To The Top

Title

Characterization and growth factor stimulation of L-arginine transport in a human colon cancer cell line.

Author

Cendan JC; Souba WW; Copeland EM 3rd; Lind DS

Address

Department of General Surgery, University of Florida College of Medicine, Gainesville 32610, USA.

Source

Ann Surg Oncol, 1995 May, 2:3, 257-65

Abstract

BACKGROUND: Epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) are potent mitogens that contribute to abnormal growth regulation in colon cancer. Growth factors have been shown to regulate transmembrane nutrient uptake as an adaptive response to support cellular proliferation. METHODS: The transport of L-arginine by the SW480 primary human colon adenocarcinoma cell line was characterized by assaying the uptake of [3H]L-arginine in the presence and absence of sodium. Kinetic studies were performed over a range of L-arginine concentrations to determine transport affinity (Km) and maximal transport velocity (Vmax). To further characterize the specific transporters, [3H]L-arginine uptake was measured in the presence of selected amino acids, hormones, and under conditions of varying external pH. To investigate the effects of EGF and TGF alpha, cells were incubated with increasing doses of growth factors (1, 10, 50 ng/ml) and L-arginine transport was measured at various time intervals (8, 12, 24 h). Proliferation was assessed by the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay 3 days after growth factor stimulation. RESULTS: The majority of carrier-mediated L-arginine transport was via a sodium-independent process (65-70%), whereas the remainder was sodium-dependent (28-30%). Diffusion contributed a small amount to total L-arginine uptake (2%). Kinetic studies of arginine transport revealed a single high-affinity Na(+)-independent transporter with a Km = 55.8 +/- 5.8 microM and a Vmax = 710.6 +/- 87.3 pM/mg protein/30 s. Na(+)-independent arginine uptake was pH-insensitive and markedly inhibited by system y+ substrates L-homoarginine, L-lysine, and L-ornithine. A single Na(+)-dependent transporter with a Km = 19.8 +/- 2.3 microM and a Vmax = 159.1 +/- 8.9 pM/mg protein/30 s was identified. Na(+)-dependent arginine uptake was inhibited by system BO,+ substrates L-lysine, L-ornithine, L-leucine, L-cysteine, and L-glutamine, but not by 2-methylaminoisobutyric acid. In addition, Na(+)-dependent arginine uptake was pH- and hormone-insensitive. Incubation with EGF or TGF alpha had no effect on Na(+)-independent L-arginine uptake; however, Na(+)-dependent uptake was enhanced 60% by EGF (10 ng/ml, p < 0.05) and 100% by TGF alpha (10 ng/ml, p < 0.05), whereas cellular proliferation was increased 27% by EGF (10 ng/ml, p < 0.05) and 37% by TGF alpha (10 ng/ml, p < 0.01). CONCLUSIONS: L-arginine transport in the SW480 colon cancer cell line is principally mediated by the Na(+)-independent system y+ and to a lesser extent by the Na(+)-dependent system BO,+. Furthermore, EGF and TGF alpha preferentially stimulate L-arginine uptake via the Na(+)-dependent transporter, ostensibly to accommodate for the mitogenic stimulus.

Language of Publication

English

Unique Identifier

95368445

MeSH Heading (Major)

Adenocarcinoma|*ME; Arginine|*PK; Colonic Neoplasms|*ME; Epidermal Growth Factor-Urogastrone|CH/*PD; Transforming Growth Factor alpha|CH/*PD

MeSH Heading

Amino Acids|PD; Carrier Proteins; Cell Division|DE; Cell Membrane Permeability|DE; Human; Hydrogen-Ion Concentration; Ion Channel Gating|DE; Nitric Oxide|BI; Radioisotopes; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Time Factors; Tumor Cells, Cultured|ME

Publication Type

JOURNAL ARTICLE

ISSN

1068-9265

Country of Publication

UNITED STATES

Record 16 from database: MEDLINE
Return To The Top

Title

Epidermal growth factor labeled beta-amanitin-poly-L-ornithine: preparation and evidence for specific cytotoxicity.

Author

Bermbach U; Faulstich H

Address

Max-Planck-Institut für medizinische Forschung, Abteilung Physiologie, Heidelberg, West Germany.

Source

Biochemistry, 1990 Jul 24, 29:29, 6839-45

Abstract

Poly-L-ornithine with an average molecular weight of 32K was reacted with beta-amanitin hydroxysuccinimide ester to form an amide-linked toxin conjugate. Loading of the polymeric chain with amanitin was high, corresponding to up to 35% of the total weight. To this amatoxin vehicle we attached a targeting molecule, human recombinant leucine-21 epidermal growth factor (hrEGFL), via a disulfide-containing linker moiety. A typical average stoichiometry of the hrEGFL labeled toxin conjugate was (L-Orn)164(beta-amanitin)19(COC2H4SSC2H4CO-hrEGFL)2. The affinity for EGF receptors of hrEGFL bound in this conjugate was tested by using A 431 cells. The affinity was eight times lower than that of unsubstituted hrEGFL but regarded as high enough for studying specific toxicity effects with cells bearing EGF receptors. We found that beta-amanitin in the labeled conjugate was able to inhibit the growth of A 431 cells at a concentration of 28 nM, 80 times lower than for native beta-amanitin and 20 times lower than for poly-L-ornithine-bound beta-amanitin without the hrEGFL label. The approximately 20-fold enhancement of cytotoxicity suggests a specific internalization of the toxin conjugate mediated by the hormone label. This idea is supported by the fact that also in another transformed fibroblast cell line, with an increased though smaller number of EGF receptors than A 431 cells, the corresponding enhancement of cytotoxicity was demonstrable but less pronounced (7-fold). The hormone-mediated increase in cytotoxicity of EGF labeled poly-L-ornithine-beta-amanitin conjugates, combined with their moderate toxicity in the mouse, encourages further examination of such compounds in tumor model systems in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Language of Publication

English

Unique Identifier

90373797

MeSH Heading (Major)

Amanitins|*/TO; Epidermal Growth Factor-Urogastrone|*/ME; Peptides|*

MeSH Heading

Animal; Cytotoxins; Human; Receptors, Epidermal Growth Factor-Urogastrone|ME; Support, Non-U.S. Gov't; Tumor Cells, Cultured|DE/ME

Publication Type

JOURNAL ARTICLE

ISSN

0006-2960

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Amanitins); 0 (Cytotoxins); 0 (Peptides); 0 (Receptors, Epidermal Growth Factor-Urogastrone); 21150-22-1 (beta-amanitin); 25104-12-5 (polyornithine); 62229-50-9 (Epidermal Growth Factor-Urogastrone)

Record 17 from database: MEDLINE
Return To The Top

Title

Role of polyamines in the growth of hormone-responsive and -resistant human breast cancer cells in nude mice.

Author

Manni A; Badger B; Martel J; Demers L

Address

Department of Medicine, Pennsylvania State University, Hershey 17033.

Source

Cancer Lett, 1992 Sep 14, 66:1, 1-9

Abstract

Recent in vitro data suggest that at least some hormone-independent breast cancer cells exhibit increased polyamine biosynthesis and resistance to antipolyamine therapy. To address this issue under conditions of in vivo growth, we tested the antiproliferative effect of the polyamine synthetic inhibitor alpha-difluoromethyl-ornithine (DFMO) on hormone-dependent (MCF-7) and -independent (MDA-MB-231, BT-20) breast cancer cell lines growing in nude mice. We observed that DFMO significantly inhibited the growth of established tumors to a similar extent in all cell lines, even though tumor regression was only observed with MCF-7 cells. DFMO, while inhibiting E2-supported MCF-7 breast cancer growth, did not inhibit E2-stimulated progesterone receptor synthesis. Cellular levels of polyamines were highest in MCF-7 cells and lowest in the BT-20 cell line. Tumor content of spermidine was similarly suppressed by DFMO treatment in the 3 cell lines, while the spermine level was unaffected. Cellular putrescine levels were suppressed in MCF-7 and BT-20 cells. Administration of DFMO prior to implantation of fragments of MCF-7 or MDA-MB-231 tumors in nude mice significantly inhibited tumor development to a similar extent. The action of DFMO seemed to be predominantly tumoristatic since new tumors develop in some mice upon discontinuation of the drug. We conclude that the hormone-independent breast cancer cell lines tested do not exhibit increased polyamine biosynthesis or resistance to antipolyamine therapy when grown in vivo in nude mice.

Language of Publication

English

Unique Identifier

93082651

MeSH Heading (Major)

Breast Neoplasms|DT/*PA/PP; Neoplasms, Hormone-Dependent|DT/*PA/PP; Polyamines|*

MeSH Heading

Animal; Cell Division|DE; Comparative Study; Drug Resistance; Drug Screening Assays, Antitumor; Eflornithine|PD; Human; Mice; Mice, Nude; Neoplasm Transplantation; Putrescine|ME/PH; Spermidine|ME/PH; Spermine|ME/PH; Support, U.S. Gov't, P.H.S.; Tumor Cells, Cultured|DE

Publication Type

JOURNAL ARTICLE

ISSN

0304-3835

Country of Publication

NETHERLANDS

CAS Registry/EC Number

0 (Polyamines); 110-60-1 (Putrescine); 124-20-9 (Spermidine); 70052-12-9 (Eflornithine); 71-44-3 (Spermine)

Record 18 from database: MEDLINE
Return To The Top

Title

Growth hormone testing for the diagnosis of growth hormone deficiency in childhood: a population register-based study.

Author

Carel JC; Tresca JP; Letrait M; Chaussain JL; Lebouc Y; Job JC; Coste J

Address

Association France Hypophyse, HÈopital Cochin, Paris, France. jccarel@infobiogen.fr

Source

J Clin Endocrinol Metab, 1997 Jul, 82:7, 2117-21

Abstract

Evaluation of GH secretion using pharmacological GH stimulation tests (GHST) remains a current practice, although the reliability of GHST has been questioned, and many pitfalls have been pointed out. We have analyzed all of the 6373 GH stimulation tests that led to the initiation of GH therapy in 3233 children treated in France from 1973-1989. Tests and GH measurements were performed by individual centers and collected by the Association France-Hypophyse. GH deficiency (GHD) was due to craniospinal irradiation (11%), was due to organic causes or associated with multiple deficiencies (22%), or was considered idiopathic (65%); 2% of the patients were considered non-GHD. Eleven different pharmacological tests were used, and 62 of the 66 theoretical pairs of tests were used at least once. The most frequent combination of tests (ornithine in one instance and insulin in another) was used in 12.7% of patients. The reliability of the GH peak measured by comparing the results of 2 tests in the same patient was poor, as measured by intraclass correlation coefficients below 0.8. Multivariate analysis identified several parameters positively or negatively associated with peak plasma GH: calendar year of initiation of treatment, etiology of GHD, height SD score, bone age SD score, puberty, weight SD score, genetic target height SD score, and the nature of the pharmacological agent used. We believe that several of these factors (weight SD score, genetic target height SD score, and nature of the agent) identify biases in the diagnosis of GHD. We conclude that GHST should be performed with a very limited number of agents, interpreted after the establishment of reference values in age-matched normal children, and associated with other clinical and biochemical parameters for establishing the diagnosis of GHD.

Language of Publication

English

Unique Identifier

97358161

MeSH Heading (Major)

Somatotropin|*BL/*DF

MeSH Heading

Adolescence; Age Factors; Child; Child, Preschool; Female; Human; Male; Methods; Registries; Reproducibility of Results; Retrospective Studies

Publication Type

JOURNAL ARTICLE

ISSN

0021-972X

Country of Publication

UNITED STATES

Record 19 from database: MEDLINE
Return To The Top

Title

Insulin induction of ornithine decarboxylase. Importance of mRNA secondary structure and phosphorylation of eucaryotic initiation factors eIF-4B and eIF-4E.

Author

Manzella JM; Rychlik W; Rhoads RE; Hershey JW; Blackshear PJ

Address

Howard Hughes Medical Institute Laboratories, Duke University Medical Center, Durham, North Carolina 27710.

Source

J Biol Chem, 1991 Feb 5, 266:4, 2383-9

Abstract

We investigated the possibility that insulin could stimulate translation of ornithine decarboxylase (ODC) mRNA in a murine fibroblast cell line that expresses large numbers of human insulin receptors (HIR 3.5 cells). Within 3 h after exposure to 70 nM insulin, ODC enzyme activity increased approximately 50-fold and mRNA accumulation 3-fold in the HIR 3.5 cells but not in normal fibroblasts. Pretreatment of cells with cycloheximide completely inhibited insulin-stimulated ODC expression; actinomycin D partially inhibited this effect. To determine the influence of the 5' untranslated region (5'UTR) of ODC mRNA on insulin-regulated ODC expression, plasmids were constructed which contained sequences from the 5'UTR of a rat ODC mRNA interposed between the ferritin promoter and the coding region of the human growth hormone gene. These constructions were then expressed transiently in HIR 3.5 cells. Insulin stimulated a 2-4-fold change in growth hormone accumulation in the medium of cells transiently expressing plasmids containing the entire 5'UTR of ODC mRNA or just the 5'-most 115 bases, a G/C-rich conserved sequence predicted to form a stem-loop structure and shown previously to be responsible for constitutive inhibition of translation. There was a direct correlation between the extent of insulin stimulation and the predicted secondary structure of the added 5'UTR sequences. To determine whether this effect might be due to insulin activation of initiation factors responsible for melting mRNA secondary structure, we examined the effect of insulin on the phosphorylation states of two such factors, eucaryotic initiation factors eIF-4B and eIF-4E. Insulin stimulated the phosphorylation of both initiation factors; this stimulation was evident at 15 min and maximal by 60 min. These results suggest a potential general mechanism by which insulin could preferentially stimulate translation of mRNAs whose 5'UTRs exhibit significant secondary structure by activating initiation factors involved in melting such secondary structures.

Language of Publication

English

Unique Identifier

91115858

MeSH Heading (Major)

Insulin|*PD; Ornithine Decarboxylase|*BI/GE; Peptide Initiation Factors|*ME; RNA, Messenger|*CH/GE

MeSH Heading

Animal; Blotting, Northern; Cell Line; Cloning, Molecular; Cycloheximide|PD; Dactinomycin|PD; Dose-Response Relationship, Drug; Enzyme Induction; Human; Mice; Nucleic Acid Conformation; Phosphorylation; Receptors, Insulin|ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Translation, Genetic

Publication Type

JOURNAL ARTICLE

ISSN

0021-9258

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 4.1.1.17 (Ornithine Decarboxylase); 0 (eIF-4B); 0 (eIF-4E); 0 (Peptide Initiation Factors); 0 (Receptors, Insulin); 0 (RNA, Messenger); 11061-68-0 (Insulin); 50-76-0 (Dactinomycin); 66-81-9 (Cycloheximide)

Record 20 from database: MEDLINE
Return To The Top
Return To The Middle Of The Menu

Title

Polyamine involvement in the growth of hormone-responsive and -resistant human breast cancer cells in culture.

Author

Glikman P; Manni A; Demers L; Bartholomew M

Address

Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.

Source

Cancer Res, 1989 Mar 15, 49:6, 1371-6

Abstract

Recent evidence indicates that hormone-responsive but not -resistant human breast cancer cells in culture are sensitive to the antiproliferative effect of the polyamine (PA) biosynthetic inhibitor alpha-difluoromethylornithine (DFMO). The present experiments were designed to investigate the potential differential involvement of the PA pathway in the growth of these different biological subtypes of human breast cancer. Thus, we evaluated the effect of DFMO on proliferation, ornithine decarboxylase (ODC) activity, and PA levels of the hormone-dependent MCF-7 and -independent MDA-MB-231 breast cancer cell lines. When tested at comparable cell density, the two cell lines had similar levels of ODC activity and PA. Administration of DFMO (0.01, 0.1, 1, 4 mM) for 6 days caused a similar dose-dependent inhibition of proliferation (up to approximately 15% of control) associated with suppression of ODC activity to undetectable levels at the highest dose. In both cell lines, putrescine and spermidine levels were maximally suppressed by doses of DFMO greater than 0.1 mM. Higher doses of DFMO (1 and 4 mM) also suppressed spermine levels to approximately 60% of control. In detailed time-course studies, DFMO administration (0.1 mM) similarly suppressed by 80% the rise in ODC observed in both cell lines following a medium change. At all time points, putrescine and spermidine levels were likewise suppressed to a similar extent. Addition of putrescine (0.1-2.5 mM) to DFMO-treated cells repleted cellular PA levels and restored growth to approximately 80% of control in both cell lines. We conclude that, under these experimental conditions, PA are similarly involved in the growth of the hormone-responsive MCF-7 and -resistant MDA-MB-231 human breast cancer cell lines.

Language of Publication

English

Unique Identifier

89168158

MeSH Heading (Major)

Biogenic Polyamines|*PH; Breast Neoplasms|*PA; Neoplasms, Hormone-Dependent|*PA

MeSH Heading

Cell Count; Dose-Response Relationship, Drug; Eflornithine|PD; Female; Human; Ornithine Decarboxylase|AN; Putrescine|PD; Support, U.S. Gov't, P.H.S.; Time Factors; Tumor Cells, Cultured

Publication Type

JOURNAL ARTICLE

ISSN

0008-5472

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 4.1.1.17 (Ornithine Decarboxylase); 0 (Biogenic Polyamines); 110-60-1 (Putrescine); 70052-12-9 (Eflornithine)

Record 21 from database: MEDLINE
Return To The Top
Return To The Middle Of The Menu

Title

Polyamine involvement in the secretion and action of TGF-alpha in hormone sensitive human breast cancer cells in culture.

Author

Kim I; Manni A; Lynch J; Demers L

Address

Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey, PA 17033.

Source

Breast Cancer Res Treat, 1991 May, 18:2, 83-91

Abstract

These experiments were designed to test polyamine (PA) involvement in the secretion and action of transforming growth factor alpha (TGF-alpha) in hormone responsive MCF-7 breast cancer cells in liquid culture. At the same time, we evaluated the influence of culture conditions (with serum vs. serum depleted) and subclonality of MCF-7 cells on PA involvement in estrogen (E2) and TGF-alpha stimulated cell proliferation. Despite inducing a profound suppression of cellular PA levels and inhibiting basal and E2-stimulated growth, administration of the PA synthesis inhibitor alpha-difluoromethylornithine (DFMO) did not influence either basal or E2-induced TGF-alpha secretion. In the same experiments, on the other hand, addition of DFMO completely blocked the growth stimulatory effect of exogenous TGF-alpha. However, when the culture conditions were changed to serum-free medium, TGF-alpha and E2-induced cell proliferation was affected modestly or not at all by DFMO administration, despite similar suppression of cellular ornithine decarboxylase (ODC) activity and PA levels. In addition, different clones of MCF-7 cells differed in their sensitivity to the antiproliferative effect of DFMO as well as in basal levels of ODC activity and PA. We conclude that PAs are not involved in basal or E2-stimulated TGF-alpha secretion in MCF-7 breast cancer cells. On the other hand, PAs do seem to be important mediators of TGF-alpha and E2-induced breast cancer cell proliferation, though the degree of such involvement appears to be influenced by serum factors and clonal variability of MCF-7 cells.

Language of Publication

English

Unique Identifier

92004007

MeSH Heading (Major)

Breast Neoplasms|*ME/PA; Polyamines|*PD; Transforming Growth Factor alpha|*SE

MeSH Heading

Cell Division|DE; Eflornithine|PD; Estrogens|PH; Human; In Vitro; Neoplasms, Hormone-Dependent; Putrescine|PD/PH; Serum Albumin, Bovine|PD; Spermidine|PH; Spermine|PH; Support, U.S. Gov't, P.H.S.; Tumor Cells, Cultured

Publication Type

JOURNAL ARTICLE

ISSN

0167-6806

Country of Publication

NETHERLANDS

CAS Registry/EC Number

0 (Estrogens); 0 (Polyamines); 0 (Serum Albumin, Bovine); 0 (Transforming Growth Factor alpha); 110-60-1 (Putrescine); 124-20-9 (Spermidine); 70052-12-9 (Eflornithine); 71-44-3 (Spermine)

Record 22 from database: MEDLINE
Return To The Top
Return To The Middle Of The Menu

Title

Failure of commercial oral amino acid supplements to increase serum growth hormone concentrations in male body-builders.

Author

Lambert MI; Hefer JA; Millar RP; Macfarlane PW

Address

Dept. of Physiology, University of Cape Town Medical School, South Africa.

Source

Int J Sport Nutr, 1993 Sep, 3:3, 298-305

Abstract

Amino acids are commonly ingested as ergogenic acids in the belief that they enhance protein synthesis and stimulate growth hormone release. The aim of this study was to determine the acute effect that amino acid supplements have on serum growth hormone (GH) concentration. Seven male body-builders reported to the laboratory on four occasions after an 8-hr fast and ingested, in random order, either a placebo, a 2.4-g arginine/lysine supplement, a 1.85-g ornithine/tyrosine supplement, or a 20-g BovrilR drink. Blood was collected before each treatment and again every 30 minutes for 3 hours for the measurement of serum GH concentration. On a separate occasion, subjects had an intravenous infusion of 0.5 microgram GH-releasing hormone.kg-1 body weight to confirm that GH secretory response was normal. The main finding was that serum GH concentrations were not altered consistently in healthy young males following the ingestion of the amino acid supplements in the quantities recommended by the manufacturers.

Language of Publication

English

Unique Identifier

94035086

MeSH Heading (Major)

Amino Acids|AD/*PD; Somatotropin|AD/BL/*DE; Weight Lifting|*PH

MeSH Heading

Administration, Oral; Adult; Human; Male; Support, Non-U.S. Gov't

Publication Type

CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL

ISSN

1050-1606

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Amino Acids); 9002-72-6 (Somatotropin)

Record 23 from database: MEDLINE
Return To The Top
Return To The Middle Of The Menu

Title

Cellular and molecular basis of intestinal and pancreatic adaptation.

Author

Dowling RH

Address

Gastroenterology Unit, Guy's Hospital, London, U.K.

Source

Scand J Gastroenterol Suppl, 1992, 193:, 64-7

Abstract

This article reviews the structural and functional changes which develop in the intestine and pancreas in response to a variety of stimuli and which characterise adaptive hyper- or hypo-plasia. It then discusses the principal physiological mechanisms controlling this adaptive growth. In the gut, these include luminal nutrition, endocrine, autocrine and paracrine hormonal influences, growth factors, enterotrophic components of pancreatico-biliary secretions, neural factors, changes in blood flow and mesenchyme-epithelial interactions. The cell biology of adaptive growth involves cell membrane receptors (first messengers) and a cascade of intracellular second messengers, the best studied of which is changes in polyamine metabolism and in related enzymes. The effects of ornithine decarboxylase (ODC) blockade with difluoromethyl ornithine (DFMO) and of diamine oxidase (DAO) blockade with aminoguanidine, are described. In general, DFMO inhibits or prevents adaptive hyperplasia while in the small bowel, aminoguanidine treatment induces 'supranormal' adaptation. However, both the gut and the pancreas transport 'exogenous' (ingested in food and circulating in the blood stream) polyamines across their apical and basolateral membranes. The influence of this exogenous polyamine transport on 'endogenous' (enzyme-regulated) intracellular polyamine concentrations, is largely unknown. Finally, the molecular biology of adaptive growth is described briefly--as illustrated by the use of a growth hormone transgenic model in which mice develop marked intestinal mucosal hyperplasia and increases in the relative abundance of insulin-like growth factor-I (IGF-I) mRNA in the intestine.

Language of Publication

English

Unique Identifier

93174201

MeSH Heading (Major)

Adaptation, Physiological|*; Intestines|ME/PA/*PH; Pancreas|ME/PA/*PH

MeSH Heading

Amine Oxidase (Copper-Containing)|ME; Animal; Cell Division; Human; Hyperplasia; Polyamines|ME; RNA, Messenger

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0085-5928

Country of Publication

NORWAY

CAS Registry/EC Number

EC 1.4.3.6 (Amine Oxidase (Copper-Containing)); 0 (Polyamines); 0 (RNA, Messenger)

Record 24 from database: MEDLINE
Return To The Top
Return To The Middle Of The Menu

Title

Effects of parathyroid hormone on ornithine decarboxylase activity in human osteosarcoma cells.

Author

Goto H; Matsui-Yuasa I; Otani S; Morisawa S; Nishizawa Y; Morii H

Address

Department of Biochemistry, Osaka City University Medical School, Japan.

Source

Arch Biochem Biophys, 1991 May 1, 286:2, 316-22

Abstract

Ornithine decarboxylase (ODC) is a rate-limiting enzyme of the biosynthesis of polyamines, which are important in cell growth and differentiation. Here, we studied whether parathyroid hormone (PTH) affects the induction of ODC and the proliferation of the human osteoblast-like cell line SaOS2, which is sensitive to PTH. In confluent cells, ODC activity was not detected, but activity was significantly induced by fresh medium, with maximum activity 6 h after the change. PTH potentiated this enzyme induction in a dose-dependent manner at 10(-9) and 10(-8) M at which range the intracellular cAMP level also rose. Dibutyryl cAMP, cholera toxin, and 3-isobutyl-1-methylxanthine each caused an increase in ODC activity similar to that with PTH. The half-life of enzyme activity was about 30 min and was not changed by the addition of PTH. mRNA coding for ODC was detected in the confluent cells and its concentration was increased two- to threefold by the fresh medium. No further increase in mRNA occurred when PTH was added. At 48 h after the change of medium, PTH inhibited the DNA synthesis induced by fresh medium. These results suggest that the increase in ODC activity caused by PTH was caused by enhancement of cAMP synthesis, and that this augmentation involves post-transcriptional regulation.

Language of Publication

English

Unique Identifier

91378318

MeSH Heading (Major)

Cyclic AMP|*ME; Ornithine Decarboxylase|*ME; Parathyroid Hormones|*PD; Peptide Fragments|*PD

MeSH Heading

Bucladesine|PD; Butyric Acids|PD; Cell Line; DNA Replication|DE; Eflornithine|PD; Human; Kinetics; Nucleic Acid Hybridization; Osteosarcoma; Polyamines|ME; RNA, Neoplasm|GE/IP

Publication Type

JOURNAL ARTICLE

ISSN

0003-9861

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 4.1.1.17 (Ornithine Decarboxylase); 0 (Butyric Acids); 0 (Parathyroid Hormones); 0 (Peptide Fragments); 0 (Polyamines); 0 (RNA, Neoplasm); 107-92-6 (butyric acid); 362-74-3 (Bucladesine); 52232-67-4 (Teriparatide); 60-92-4 (Cyclic AMP); 70052-12-9 (Eflornithine)

Record 25 from database: MEDLINE
Return To The Top
Return To The Middle Of The Menu

Title

Variations in amplification and expression of the ornithine decarboxylase gene in human breast cancer cells.

Author

Thomas T; Kiang DT; Jänne OA; Thomas TJ

Address

Department of Environmental and Community Medicine, UMDNJ-Robert Wood Johnson Medical School, Piscataway 08854.

Source

Breast Cancer Res Treat, 1991 Nov, 19:3, 257-67

Abstract

The polyamine biosynthetic pathway plays a critical role in the growth of human breast cancer cells. Ornithine decarboxylase (ODC) is a key enzyme in polyamine biosynthesis. To understand the regulation of ODC activity and polyamine accumulation in breast cancer cells, we studied amplification and expression of the ODC gene in four breast cancer cell lines. ODC gene dosage was analyzed by Southern blot hybridization and was 4- to 12-fold higher in T-47D, MDA-MB-231, and BT-20 cell lines than in the MCF-7 cell line. ODC mRNA level was 2- to 3-fold higher in BT-20 and MDA-MB-231 cell lines than in the other two lines. We also measured ODC activity and polyamine concentration in these cell lines, and determined their sensitivity to an ODC inhibitor, difluoromethylornithine (DFMO). BT-20 cells showed significantly higher ODC activity and polyamine concentrations than the other three cell lines. BT-20 cells were resistant to the growth inhibitory effect of DFMO even at 4 mM concentration, whereas the proliferation of MCF-7, T47D, and MDA-MB-231 cells was inhibited by this drug. These results suggest that different transcriptional and post-transcriptional mechanisms control the regulation of ODC gene expression in breast cancer cell lines.

Language of Publication

English

Unique Identifier

92135858

MeSH Heading (Major)

Adenocarcinoma|EN/*PA; Breast Neoplasms|EN/*PA; Carcinoma|EN/*PA; Carcinoma, Intraductal, Noninfiltrating|EN/*PA; Neoplasm Proteins|BI/*GE; Ornithine Decarboxylase|BI/*GE

MeSH Heading

Comparative Study; DNA, Neoplasm|GE; Eflornithine|PD; Enzyme Induction; Estrogens; Female; Gene Amplification; Gene Expression Regulation, Neoplastic; Human; Neoplasms, Hormone-Dependent|EN/PA; Polyamines|AN; RNA, Messenger|BI; RNA, Neoplasm|AN; Support, U.S. Gov't, P.H.S.; Tumor Cells, Cultured|DE/EN

Publication Type

JOURNAL ARTICLE

ISSN

0167-6806

Country of Publication

NETHERLANDS

CAS Registry/EC Number

EC 4.1.1.17 (Ornithine Decarboxylase); 0 (DNA, Neoplasm); 0 (Estrogens); 0 (Neoplasm Proteins); 0 (Polyamines); 0 (RNA, Messenger); 0 (RNA, Neoplasm); 70052-12-9 (Eflornithine)

Record 26 from database: MEDLINE
Return To The Top
Return To The Middle Of The Menu

Title

Comparison of growth hormone response to growth hormone-releasing factor 1-44 according to the combined study of sleep secretion with the responses to pharmacologic stimuli.

Author

Garnier P; Liapi C; Raynaud F; Evain-Brion D

Address

Fondation de Recherche en Hormonologie, Fresnes, France.

Source

Horm Res, 1987, 28:1, 13-9

Abstract

The growth hormone (GH) response to GH-releasing factor (GRF) was studied in 54 severely growth-retarded patients (-2.1 to -6.5 SD) aged from 5 to 20 years (32 males and 22 females), among whom 34 were prepubertal and 20 at early pubertal stages. The patients were also submitted to a standard evaluation of their GH secretion, consisting of at least two classical pharmacologic stimulation (CPS) tests, such as ornithine, arginine and/or insulin, and one study of the GH sleep secretion (SS). The results of the standard evaluation allowed to distinguish 5 groups: (I) endocrinologically normal (n = 26); (II) completely GH deficient (n = 5); (III) partially GH deficient (n = 8); (IV) dissociated GH secretions with normal SS (n = 9), and (V) dissociated GH secretions with low SS (n = 6). The GH responses to GRF were correlated with both responses to CPS and SS. There was a large overlap of the individual responses to GRF between the 5 groups, but the mean responses in groups II, IV and V were significantly lower than in group I. Furthermore, the mean responses of groups IV and V were in the lower range of the normal. It is concluded that the GRF test may be useful to ascertain the diagnosis of functional or partial GH deficiency when the responses to CPS and SS are dissociated.

Language of Publication

English

Unique Identifier

88197053

MeSH Heading (Major)

Growth Disorders|*ME; Sleep|*PH; Somatotropin|DF/*SE; Somatotropin-Releasing Hormone|*DU

MeSH Heading

Adolescence; Adult; Child; Child, Preschool; Comparative Study; Female; Human; Male; Pituitary Function Tests|MT; Pituitary Gland|DE/SE

Publication Type

JOURNAL ARTICLE

ISSN

0301-0163

Country of Publication

SWITZERLAND

CAS Registry/EC Number

9002-72-6 (Somatotropin); 9034-39-3 (Somatotropin-Releasing Hormone)

Record 27 from database: MEDLINE
Return To The Top
Return To The Middle Of The Menu

Title

Statistical study of 5473 results of nine pharmacological stimulation tests: a proposed weighting index.

Author

Rochiccioli P; Enjaume C; Tauber MT; Pienkowski C

Address

Service de Pédiatrie, CHU Purpan, Toulouse, France.

Source

Acta Paediatr, 1993 Mar, 82:3, 245-8

Abstract

A total of 5473 pharmacological stimulation tests were carried out in 3143 children and subjected to statistical analysis. The mean chronological age of the children was 9 years 9 months (range 3 years to 16 years 6 months) and mean bone age was 7 years 6 months (range 2 years to 14 years). Nine pharmacological tests were used: (1) arginine (n = 625); (2) clonidine (n = 339); (3) insulin (n = 198); (4) ornithine (n = 162); (5) insulin and arginine (n = 203); (6) clonidine and betaxolol (n = 2003); (7) L-dopa (n = 685); (8) glucagon and propranolol (n = 443); and (9) glucagon and betaxolol (n = 815). Measurement of plasma growth hormone was always performed using the same method. The distribution of values in each test was of the gausso-logarithmic type. The results of the mean peak and the 95% confidence limit were as follows: (1) 10.2, 0.45; (2) 11.5, 0.7; (3) 11.8, 0.8; (4) 14.2, 1.2; (5) 14.3, 0.9; (6) 15.7, 1.1; (7) 19.8, 2.1; (8) 20.8, 2.3; (9) 21, 2.5. These results lead to the following conclusions: the specificity of these tests is low, the mean peak may vary two-fold from one test to another, and the percentage of peaks < 10 ng/ml ranges from 69% for test 1 to 29% for tests 8 and 9. The proportion of growth hormone deficiencies thus varies considerably according to the test used.(ABSTRACT TRUNCATED AT 250 WORDS)

Language of Publication

English

Unique Identifier

93264725

MeSH Heading (Major)

Drugs|*DU; Growth Disorders|BL/*DI

MeSH Heading

Adolescence; Child; Child, Preschool; Comparative Study; Female; Human; Male; Retrospective Studies; Sensitivity and Specificity; Somatotropin|BL/DF

Publication Type

JOURNAL ARTICLE

ISSN

0803-5253

Country of Publication

NORWAY

CAS Registry/EC Number

0 (Drugs); 9002-72-6 (Somatotropin)

Record 28 from database: MEDLINE
Return To The Top
Return To The Middle Of The Menu

Title

Human promyelocytic cell line HL60 has the specific binding sites for prolactin and its ornithine decarboxylase, DNA synthesis and cellular proliferation are induced by prolactin.

Author

Nishiguchi Y; Hibasami H; Komada Y; Sakurai M; Nakashima K

Address

Department of Biochemistry, Mie University Faculty of Medicine, Japan.

Source

Leuk Res, 1993 Aug, 17:8, 633-7

Abstract

Human prolactin (hPRL) induced ornithine decarboxylase (ODC) activity, subsequently DNA synthesis and cellular proliferation on human promyelocytic cells, HL60, cultured in a serum-free medium. HL60 cells had 2100 specific binding sites for hPRL per cell, showing a dissociation constant of 1.1 x 10(-10) M. Binding of 125I-PRL to the cells was not blocked by simultaneous addition of human growth hormone. ODC activity and DNA synthesis were activated maximally at 5 and 20 h, respectively, after the addition of 0.05 nM hPRL. These effects of PRL on cellular proliferation, ODC activity and DNA synthesis were abolished by the simultaneous addition of anti-hPRL antibody. Simultaneous addition of an irreversible inhibitor of ODC, difluoromethyl ornithine (DFMO), also abolished the inductions of ODC and DNA synthesis by hPRL. The inhibitory effect of DFMO on hPRL-induced DNA synthesis was reversed by the addition of putrescine to the culture medium. These results suggest that hPRL binds to the prolactin receptor on HL60 cells and induces ODC activity to increase cellular polyamine levels, which eventually stimulates DNA synthesis and cellular proliferation.

Language of Publication

English

Unique Identifier

93360545

MeSH Heading (Major)

Cell Division|*DE; DNA Replication|*DE; Leukemia, Promyelocytic, Acute|*ME/PA; Ornithine Decarboxylase|*BI; Prolactin|ME/*PD; Receptors, Prolactin|*BI

MeSH Heading

Binding Sites; Carbon Radioisotopes; Dose-Response Relationship, Drug; DNA, Neoplasm|BI; Enzyme Induction; Human; Iodine Radioisotopes; Kinetics; Thymidine|ME; Tritium; Tumor Cells, Cultured

Publication Type

JOURNAL ARTICLE

ISSN

0145-2126

Country of Publication

ENGLAND

CAS Registry/EC Number

EC 4.1.1.17 (Ornithine Decarboxylase); 0 (Carbon Radioisotopes); 0 (DNA, Neoplasm); 0 (Iodine Radioisotopes); 0 (Receptors, Prolactin); 10028-17-8 (Tritium); 50-89-5 (Thymidine); 9002-62-4 (Prolactin)

Record 29 from database: MEDLINE
Return To The Top
Return To The Middle Of The Menu

Title

Retinoic acid regulates ornithine decarboxylase gene expression at the transcriptional level.

Author

Mao Y; Gurr JA; Hickok NJ

Address

Department of Dermatology, Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PA 19107.

Source

Biochem J, 1993 Nov 1, 295 ( Pt 3):, 641-4

Abstract

Retinoic acid (RA) is important for normal mammalian development and growth. Ornithine decarboxylase (ODC) is the first and rate-limiting enzyme in the biosynthesis of the polyamines, and we have previously shown that ODC mRNA levels are suppressed by RA in human skin cells. Using HeLa cells, we now show that treatment with 0.5 microM RA for 24 h suppresses endogenous ODC mRNA levels and the expression of a transfected ODC/chloramphenicol acetyltransferase plasmid (Kpn-ODCCAT), containing sequences from -1450 to +810 of the human ODC gene. Co-transfection with either the alpha-RA receptor (alpha-RAR) or a chimeric alpha-RA/oestrogen receptor (alpha-RAER) followed by treatment with the cognate hormone suppresses expression of Kpn-ODCCAT and Not-ODCCAT, which contains sequences from -250 to +514. Liganded alpha-RAR suppresses the activity of Kpn-ODCCAT more markedly than does liganded alpha-RAER (98% and 80% suppression, respectively), whereas both receptors have very similar effects on Not-ODCCAT expression (73% and 67% suppression, respectively). The unliganded alpha-RAR suppresses Kpn-ODCCAT by 76%, whereas unliganded alpha-RAER has no significant effect. These data show that RA regulates ODC-gene expression at the transcriptional level, and that alpha-RAR, but not alpha-RAER, can confer full hormonal responsiveness. This suggests that the activating function present in the alpha-RAR ligand-binding domain is required for full transcriptional regulation.

Language of Publication

English

Unique Identifier

94059011

MeSH Heading (Major)

Gene Expression Regulation|*DE; Ornithine Decarboxylase|*GE; Transcription, Genetic|*DE; Tretinoin|*PD

MeSH Heading

Animal; Blotting, Northern; Cell Line; Cercopithecus aethiops; Hela Cells; Human; Kidney; Receptors, Estrogen|GE/PH; Receptors, Retinoic Acid|GE/PH; RNA, Messenger|ME; Support, U.S. Gov't, P.H.S.; Transfection

Publication Type

JOURNAL ARTICLE

ISSN

0264-6021

Country of Publication

ENGLAND

CAS Registry/EC Number

EC 4.1.1.17 (Ornithine Decarboxylase); 0 (Receptors, Estrogen); 0 (Receptors, Retinoic Acid); 0 (RNA, Messenger); 302-79-4 (Tretinoin)

Record 30 from database: MEDLINE
Return To The Top
Return To The Middle Of The Menu

Title

Low-dose amino acid supplementation: no effects on serum human growth hormone and insulin in male weightlifters.

Author

Fogelholm GM; Näveri HK; Kiilavuori KT; Härkönen MH

Address

Dept. of Applied Chemistry and Microbiology, University of Helsinki, Finland.

Source

Int J Sport Nutr, 1993 Sep, 3:3, 290-7

Abstract

Using a double-blind, crossover protocol, we studied the possible effects of a 4-day combined L-arginine, L-ornithine, and L-lysine supplementation (each 2 g/day, divided into two daily doses) on 24-hr level of serum human growth hormone (hGH) and insulin in 11 competitive weightlifters, ages 19 to 35 yrs. Three similar daily hGH peaks, seemingly preceded by a decrease in serum insulin concentration, were found during both amino acid and placebo supplementation. Supplementation did not affect the physiological variation of serum hGH concentration (treatment and treatment x time interaction: p = 0.43-0.55). Analogously, serum insulin levels were not higher after amino acid supplementation. Therefore the ergogenic value of low-dose oral amino acid supplementation in increasing hGH or insulin secretion seems questionable.

Language of Publication

English

Unique Identifier

94035085

MeSH Heading (Major)

Amino Acids|AD/*PD; Somatotropin|BL/*DE; Weight Lifting|*PH

MeSH Heading

Adult; Double-Blind Method; Drug Administration Schedule; Human; Insulin|ME; Male; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE

ISSN

1050-1606

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Amino Acids); 11061-68-0 (Insulin); 9002-72-6 (Somatotropin)

Record 31 from database: MEDLINE
Return To The Top
Return To The Middle Of The Menu

Title

Analogues of luteinizing hormone-releasing hormone containing cytotoxic groups.

Author

Janáky T; Juhász A; Bajusz S; Csernus V; Srkalovic G; Bokser L; Milovanovic S; Redding TW; Rékási Z; Nagy A; et al

Address

Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New Orleans, LA.

Source

Proc Natl Acad Sci U S A, 1992 Feb 1, 89:3, 972-6

Abstract

In an attempt to produce better cytotoxic analogues, chemotherapeutic antineoplastic radicals including an alkylating nitrogen mustard derivative of D-phenylalanine (D-melphalan), reactive cyclopropane, anthraquinone derivatives [2-(hydroxymethyl)anthraquinone and the anticancer antibiotic doxorubicin], and an antimetabolite (methotrexate) were coupled to suitably modified agonists and antagonists of luteinizing hormone-releasing hormone (LH-RH). Analogues with D-lysine6 and D-ornithine6 or N epsilon-(2,3-diaminopropionyl)-D-lysine and N delta-(2,3-diaminopropionyl)-D-ornithine were used as carriers for one or two cytotoxic moieties. The enhanced biological activities produced by the incorporation of D amino acids into position 6 of the agonistic analogues were further increased by the attachment of hydrophobic cytotoxic groups, resulting in compounds with 10-50 times higher activity than LH-RH. Most of the monosubstituted agonistic analogues showed high affinities for the membrane receptors of human breast cancer cells, while the receptor binding affinities of peptides containing two cytotoxic side chains were lower. Antagonistic carriers [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3, Arg5,D-Lys6,D-Ala10] LH-RH [where Nal(2) is 3-(2-naphthyl)alanine], [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3,Arg5,N epsilon-(2,3-diaminopropionyl)-D-Lys6,D- Ala10]LH-RH, and their D-Pal(3)3 homologs [Pal(3) is 3-(3-pyridyl)alanine] as well as [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Pal(3)3,Tyr5,N epsilon-(2,3-diamino-propionyl)-D-Lys6,D-Ala10]LH-RH were linked to cytotoxic compounds. The hybrid molecules inhibited ovulation in rats at doses of 10 micrograms and suppressed LH release in vitro. The receptor binding of cytotoxic analogues was decreased compared to the precursor peptides, although analogues with 2-(hydroxymethyl)anthraquinone hemiglutarate had high affinities. All of the cytotoxic analogues tested inhibited [3H]thymidine incorporation into DNA in cultures of human breast and prostate cancer cell lines. Some cytotoxic analogues also significantly suppressed the growth of mammary and prostate cancers in vivo in animal models.

Language of Publication

English

Unique Identifier

92141240

MeSH Heading (Major)

Cytotoxins|*AD; Gonadorelin|*AA/ME; Hormones, Synthetic|*CH

MeSH Heading

Amino Acid Sequence; Animal; Antimetabolites, Antineoplastic|AD; Cell Division|DE; Human; In Vitro; Molecular Sequence Data; Rats; Receptors, LHRH|ME; Structure-Activity Relationship; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Tumor Cells, Cultured

Publication Type

JOURNAL ARTICLE

ISSN

0027-8424

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Antimetabolites, Antineoplastic); 0 (Cytotoxins); 0 (Hormones, Synthetic); 0 (Receptors, LHRH); 33515-09-2 (Gonadorelin)

Record 32 from database: MEDLINE
Return To The Top
Return To The Middle Of The Menu

Title

Role of gastrin as a trophic hormone.

Author

Walsh JH

Address

Center for Ulcer Research and Education, Wadsworth Veterans Administration Center, Los Angeles, Calif.

Source

Digestion, 1990, 47 Suppl 1:, 11-6; discussion 49-52

Abstract

Gastrin has two principal biological effects: stimulation of acid secretion from gastric parietal cells and stimulation of mucosal growth in the acid-secreting part of the stomach. Circulating gastrin regulates the increase in acid secretion that occurs during the after meals. Gastrin also stimulates mucosal growth in the stomach. Exogenously administered gastrin causes increased cell division in the proliferative zone that lies between the surface cells and the gastric glands in the acid-secreting mucosa. The newly formed cells undergo differentiation into surface epithelial cells, parietal cells and gastric enterochromaffin-like cells. Furthermore, the increased mucosal proliferation that occurs with refeeding after a period of fasting may be mediated by gastrin since refeeding stimulates gastrin production and a parallel increase in mucosal DNA synthesis. Both food and gastrin cause a rapid increase in cell division and an increase in gastric ornithine decarboxylase mRNA in fasting rats. In preliminary immunoneutralization experiments, the stimulation of ornithine decarboxylase produced by food was inhibited by gastrin antibody. The sustained inhibition of gastric acid secretion obtained by surgery or with antisecretory drug therapy results in hypergastrinaemia associated with increased gastric mucosal cell proliferation. A good correlation between gastric enterochromaffin-like cell density and circulating gastrin concentrations has been found under these conditions as well as during infusions of exogenous gastrin. Trophic effects of gastrin have also been reported for the colon, duodenum and pancreas, but chronic hypergastrinaemia does not appear to produce hyperplasia of these organs.(ABSTRACT TRUNCATED AT 250 WORDS)

Language of Publication

English

Unique Identifier

91231139

MeSH Heading (Major)

Gastric Acid|*SE; Gastrins|PD/*PH; Parietal Cells, Gastric|*SE

MeSH Heading

Animal; Cell Division|DE; Gastric Mucosa|CY/DE; Human; Omeprazole|PD

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0012-2823

Country of Publication

SWITZERLAND

CAS Registry/EC Number

0 (Gastrins); 73590-58-6 (Omeprazole)

Record 33 from database: MEDLINE
Return To The Top
Return To The Middle Of The Menu

Title

Regulation of rat ornithine decarboxylase mRNA translation by its 5'-untranslated region.

Author

Manzella JM; Blackshear PJ

Address

Howard Hughes Medical Institute Laboratories, Duke University Medical Center, Durham, North Carolina 27710.

Source

J Biol Chem, 1990 Jul 15, 265:20, 11817-22

Abstract

Ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis, is a highly inducible protein whose expression involves a complex and variable array of regulatory mechanisms. We investigated the influence of the 5'-untranslated region (5'UTR) of the rat ODC mRNA on translation of the mRNA in a cell-free system and in cultured mammalian cells. ODC mRNA containing the full-length 5'UTR was translated in reticulocyte lysates at approximately 5% of the rate of mRNA containing no ODC 5' leader sequences. The complete 5'UTR inhibited expression of a heterologous gene product, human growth hormone, to the same extent in cultured mammalian cells. Furthermore, the 5'-most 130 bases of the rat ODC 5'UTR, a conserved G/C-rich region predicted to form a stable stem-loop structure (delta G = -68 kcal/mol), repressed translation to the same extent as the entire 5'UTR, both in the lysates and in intact cells. The 3'-most 160 bases of the 5'UTR, containing a small upstream open reading frame, decreased expression by 50-65% both in vitro and in intact cells, compared with controls lacking any ODC 5'UTR sequences. Mutation of the initiation codon AUG beginning this upstream open reading frame to GCG restored expression to rates equivalent to those seen in constructions containing no ODC 5'UTR sequences. We conclude that the rat ODC mRNA 5'UTR can inhibit translation of ODC mRNA both in vitro and in vivo, and that the predicted stem-loop structure at the 5' end of the 5'UTR is both necessary and sufficient for this inhibition.

Language of Publication

English

Unique Identifier

90307705

MeSH Heading (Major)

Gene Expression Regulation, Enzymologic|*; Ornithine Decarboxylase|*GE; RNA, Messenger|*GE; Translation, Genetic|*

MeSH Heading

Animal; Calorimetry; Cell Line; Cells, Cultured; Genes, Regulator; Human; Kinetics; Mice; Mutation; Nucleic Acid Conformation; Plasmids; Promoter Regions (Genetics); Rats; Restriction Mapping; Reticulocytes|ME; Somatotropin|AN/GE; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Transfection

Publication Type

JOURNAL ARTICLE

ISSN

0021-9258

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 4.1.1.17 (Ornithine Decarboxylase); 0 (Plasmids); 0 (RNA, Messenger); 9002-72-6 (Somatotropin)

Record 34 from database: MEDLINE
Return To The Top
Return To The Middle Of The Menu

Title

Direct analysis of growth factor requirements for isolated human fetal hepatocytes.

Author

Hoshi H; Kan M; McKeehan WL

Address

W. Alton Jones Cell Science Center, Inc., Lake Placid, New York 12946.

Source

In Vitro Cell Dev Biol, 1987 Oct, 23:10, 723-32

Abstract

Hepatocytes were isolated from human fetal liver in order to analyze the direct effects of growth factors and hormones on human hepatocyte proliferation and function. Mechanical fragmentation and then dissociation of fetal liver tissue with a collagenase/dispase mixture resulted in high yield and viability of hepatocytes. Hepatocytes were selected in arginine-free, ornithine-supplemented medium and defined by morphology, albumin production and ornithine uptake into cellular protein. A screen of over twenty growth factors, hormones, mitogenic agents and crude organ and cell extracts for effect on the stimulation of hepatocyte growth revealed that EGF, insulin, dexamethasone, and factors concentrated in bovine neural extract and hepatoma cell-conditioned medium supported attachment, maintenance and growth of hepatocytes on a collagen-coated substratum. The population of cells selected and defined as differentiated hepatocytes had a proliferative potential of about 4 cumulative population doublings. EGF and insulin synergistically stimulated DNA synthesis in the absence of other hormones and growth factors. Although neural extracts enhanced hepatocyte number, no effect on DNA synthesis of neural extracts or purified heparin-binding growth factors from neural extracts could be demonstrated in the absence or presence of defined hormones, hepatoma-conditioned medium or serum. Hepatoma cell-conditioned medium had the largest impact on both hepatocyte cell number and DNA synthesis under all conditions. Dialyzed serum protein (1 mg/ml) at 10 times higher protein concentration had a similar effect to hepatoma cell-conditioned medium (100 micrograms/ml). The results suggest that hepatoma cell conditioned medium may be a concentrated and less complicated source than serum for purification and characterization of additional normal hepatocyte growth factors.

Language of Publication

English

Unique Identifier

88032740

MeSH Heading (Major)

Growth Substances|*PD; Hormones|*PD; Liver|CY/DE/*EM

MeSH Heading

alpha-Fetoproteins|AN; Albumins|AN; Arginine|PD; Blood|PH; Cell Adhesion|DE; Cell Division|DE; Cell Survival; Cells, Cultured; Comparative Study; Culture Media|PD; Drug Interactions; Human; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE

ISSN

0883-8364

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (alpha-Fetoproteins); 0 (Albumins); 0 (Culture Media); 0 (Growth Substances); 0 (Hormones); 7004-12-8 (Arginine)

Record 35 from database: MEDLINE
Return To The Top
Return To The Middle Of The Menu

Title

Regulation of ornithine decarboxylase gene expression in MCF-7 breast cancer cells by antiestrogens.

Author

Thomas T; Trend B; Butterfield JR; Jänne OA; Kiang DT

Address

Department of Environmental and Community Medicine, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway 08854.

Source

Cancer Res, 1989 Nov 1, 49:21, 5852-7

Abstract

Ornithine decarboxylase (ODC) is an enzyme intimately related to cell growth regulation. The metabolic products of ODC, the polyamines, are known to play a vital role in the structure and function of biological macromolecules including nucleic acids and proteins. The activity of ODC is stimulated by estrogens in their target cells. In order to gain insight into the molecular mechanism of action of antiestrogens in human breast cancer, we studied the effect of tamoxifen and 4-hydroxytamoxifen on the concentration of ODC mRNA, ODC activity, and the polyamine levels in a hormone-responsive breast cancer cell line, MCF-7. ODC mRNA concentration was reduced to 40% of the controls after 6 h of treatment of the cells with 100 nM 4-hydroxytamoxifen, but tamoxifen had no significant effect on ODC mRNA after treating with even 1 microM concentration for 36 h. ODC activity was, however, reduced to 40 and 75% of the controls after 24 h of treatment with 4-hydroxytamoxifen and tamoxifen, respectively. There was a significant reduction in the concentration of putrescine to 63% of control in tamoxifen-treated cells, but spermidine and spermine levels were not affected. With 4-hydroxytamoxifen, putrescine, spermidine, and spermine levels were reduced to 41, 62, and 79% of the control, respectively. In addition, exogenous putrescine was able to reverse the growth inhibitory effects of 4-hydroxytamoxifen. Overall, these results indicate that ODC and polyamine levels in MCF-7 cells are controlled by antiestrogens, and that suppression of polyamine biosynthesis plays a critical role in the growth inhibitory effects of antiestrogens.

Language of Publication

English

Unique Identifier

90002952

MeSH Heading (Major)

Breast Neoplasms|*EN; Estrogen Antagonists|*PD; Gene Expression Regulation, Enzymologic|*DE; Gene Expression Regulation, Neoplastic|*DE; Genes, Structural|*DE; Ornithine Decarboxylase|BI/*GE

MeSH Heading

Blotting, Northern; Cell Line; Female; Human; Nucleic Acid Hybridization; Polyamines|ME; Putrescine|PD; RNA, Messenger|DE/GE; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tamoxifen|PD; Tumor Cells, Cultured|DE

Publication Type

JOURNAL ARTICLE

ISSN

0008-5472

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 4.1.1.17 (Ornithine Decarboxylase); 0 (Estrogen Antagonists); 0 (Polyamines); 0 (RNA, Messenger); 10540-29-1 (Tamoxifen); 110-60-1 (Putrescine); 68392-35-8 (4-hydroxytamoxifen)

Record 36 from database: MEDLINE
Return To The Top

Return To The Middle Of The Menu

Title

Involvement of the polyamine pathway in antiestrogen-induced growth inhibition of human breast cancer.

Author

Cohen FJ; Manni A; Glikman P; Bartholomew M; Demers L

Address

Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.

Source

Cancer Res, 1988 Dec 1, 48:23, 6819-25

Abstract

Recent evidence indicates that the antiestrogen tamoxifen (TAM) may inhibit breast cancer cell proliferation, at least in part, through suppression of the polyamine (PA) pathway. To directly test this hypothesis, we evaluated the effect of TAM administration on ornithine decarboxylase (ODC) activity, the rate-limiting enzyme in PA synthesis, as well as cellular PA levels in the hormone-responsive MCF-7 breast cancer cell line in culture. In detailed time course studies, we observed that TAM significantly inhibited the rise in ODC activity observed in control cells following a medium change. Chronic treatment with escalating amounts of TAM caused a dose-related decrease in tumor pools of putrescine and spermidine, while spermine levels were unaffected. The TAM effects on ODC activity and PA pools were reversible with exogenous estradiol administration. However, addition of putrescine to TAM-treated cells did not result in a reversal of the antiproliferative effect of TAM, despite repletion of cellular PA pools. Administration of TAM to the hormone-independent MDA-MB-231 breast cancer cell line did not suppress ODC activity or cellular PA levels despite induction, at high concentrations, of an estradiol-irreversible inhibition of proliferation. We conclude that, in the hormone-responsive MCF-7 breast cancer cell line, TAM causes a significant suppression of the PA pathway, the relation of which, if any, to its antiproliferative action remains obscure. This effect seems to be mediated through the estrogen receptor and does not appear to be a nonspecific consequence of inhibition of cell proliferation.

Language of Publication

English

Unique Identifier

89028354

MeSH Heading (Major)

Biogenic Polyamines|*ME; Breast Neoplasms|EN/*PA; Tamoxifen|*PD

MeSH Heading

Cell Division|DE; Dose-Response Relationship, Drug; Estradiol|PD; Female; Human; Ornithine Decarboxylase|ME; Polyamines|PD; Support, U.S. Gov't, P.H.S.; Tumor Cells, Cultured

Publication Type

JOURNAL ARTICLE

ISSN

0008-5472

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 4.1.1.17 (Ornithine Decarboxylase); 0 (Biogenic Polyamines); 0 (Polyamines); 10540-29-1 (Tamoxifen); 50-28-2 (Estradiol)

Record 37 from database: MEDLINE
Return To The Top
Return To The Middle Of The Menu

Title

Intestinal adaptation in short-bowel syndrome.

Author

Lentze MJ

Address

Abteilung für pädiatrische Gastroenterologie, Medizinische Universitäts-Kinderklinik, Bern, Switzerland.

Source

Eur J Pediatr, 1989 Jan, 148:4, 294-9

Abstract

After massive resection of the small intestine the remnant mucosa has an important capacity to enlarge the absorptive surface for the digestion, hydrolysis and absorption of nutrients. This intestinal adaptation is achieved by the interaction of various factors. Oral nutrients together with pancreatic biliary secretions stimulate the mucosa to become hyperplastic. Secondary to these luminal factors hormones play an important role in the adaptive process. Among the hormones, enteroglucagon is the most important growth promoting agent together with other growth factors such as epidermal growth factor, prostaglandin E2 and human growth hormone analogues, e.g. plerocercoid growth factor from the plerocercoid larvae of the tapeworm Spirometra mansonoides. The intestinal enterocyte is the target of these factors and within the cell the synthesis of polyamines, which are responsible for rapid growth, is the most essential step for the development of hyperplasia after resection. The rate limiting enzyme for polyamine synthesis ornithine decarboxylase (ODC) reacts to trophic stimuli with an increased activity. Thereafter rapid accumulation of tissue polyamines occurs. Blockade of ODC by specific inhibitors is accompanied by absence of intestinal hyperplasia after resection. Therefore it is concluded that ODC plays a key role in the intestinal adaptation of the remnant small bowel. To start and enhance intestinal hyperplasia after resection in patients with short bowel syndrome introduction of oral nutrition as soon as possible after operation is very important. On account of gastric acid hypersecretion the use of H2 receptor blocking agents is recommended. A decreased intestinal transit time is treated with loperamide.(ABSTRACT TRUNCATED AT 250 WORDS)

Language of Publication

English

Unique Identifier

89210965

MeSH Heading (Major)

Intestinal Absorption|*; Malabsorption Syndromes|*PP; Short Bowel Syndrome|*PP

MeSH Heading

Child; Human; Intestinal Mucosa|PP

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0340-6199

Country of Publication

GERMANY, WEST

Record 38 from database: MEDLINE
Return To The Top
Return To The Middle Of The Menu

Title

Effects of estradiol on proliferation of endometrial adenocarcinoma cells (Ishikawa line).

Author

Holinka CF; Hata H; Gravanis A; Kuramoto H; Gurpide E

Address

 

Source

J Steroid Biochem, 1986 Nov, 25:5B, 781-6

Abstract

Estradiol (E2) stimulates the proliferation of human endometrial adenocarcinoma cells of the Ishikawa line, which had been previously shown to respond to estrogen by increasing their levels of progesterone receptor and the specific activities of DNA polymerase alpha and alkaline phosphatase. Although E2 (10(-8) M) did not increase rates of proliferation during the initial logarithmic growth period of the cultures under the chosen experimental conditions (MEM with 15% charcoal-treated fetal bovine serum renewed every 2-3 days), it sustained cell proliferation after about day 10, when parallel control cultures had reached plateau cell densities. Cell proliferation in control cultures at plateau levels was resumed when the hormone was added. Growth rates of cultures containing E2 from the time of seeding and the proportion of quiescent cells, estimated by using a simple cell kinetic model, decreased steadily with time. Ornithine decarboxylase and DNA polymerase alpha activities, as well as estrogen receptor levels, also decreased with time in culture. Ishikawa cells formed colonies in soft agar; colony formation efficiencies were higher as the number of cells seeded was increased from 10,000 to 100,000 cells/6 cm dish, were not influenced by the addition of E2 to the medium (10(-9) to 10(-5) M) and were markedly reduced by difluoromethylornithine (10(-2) M), an effect that was counteracted by putrescine (25 X 10(-6) M).

Language of Publication

English

Unique Identifier

87113988

MeSH Heading (Major)

Adenocarcinoma|ME/*PA; Estradiol|*PD; Uterine Neoplasms|ME/*PA

MeSH Heading

Cell Division|DE; Cell Line; DNA Polymerase II|ME; Female; Human; Kinetics; Mathematics; Models, Biological; Ornithine Decarboxylase|ME; Receptors, Estrogen|ME; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE

ISSN

0022-4731

Country of Publication

ENGLAND

CAS Registry/EC Number

EC 2.7.7.- (DNA Polymerase II); EC 4.1.1.17 (Ornithine Decarboxylase); 0 (Receptors, Estrogen); 50-28-2 (Estradiol)

Record 39 from database: MEDLINE
Return To The Top
Return To The Middle Of The Menu

Title

Sensory deprivation stress and supplemental stimulation in the rat pup and preterm human neonate.

Author

Schanberg SM; Field TM

Address

Pharmacology Department, Duke University Medical School, Durham, NC 27710.

Source

Child Dev, 1987 Dec, 58:6, 1431-47

Abstract

This article reviews the literature and presents data from our laboratories on sensory deprivation stress and supplemental stimulation of the rat pup and the preterm neonate. The data suggest that the effects of maternal deprivation in the rat pup (suppression of growth hormone release and protein synthesis) are regulated by a specific form of tactile stimulation: only brush stroking of maternally deprived rat pups returned growth parameters to normal; other forms of stimulation, including kinesthetic and vestibular stimulation, were ineffective in restoring normal functions. Other data are presented demonstrating that very small preterm neonates given tactile-kinesthetic stimulation gain more weight per day, spend more time awake and active, and show more mature habituation, orientation, motor, and range of state behaviors on the Brazelton assessment.

Language of Publication

English

Unique Identifier

88081823

MeSH Heading (Major)

Animals, Newborn|*PH; Infant, Premature|*PH; Sensory Deprivation|*PH

MeSH Heading

Animal; Arousal|PH; Body Weight; Human; Infant, Newborn; Kinesthesis|PH; Ornithine Decarboxylase|ME; Rats; Somatotropin|ME; Support, U.S. Gov't, P.H.S.; Touch|PH

Publication Type

JOURNAL ARTICLE

ISSN

0009-3920

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 4.1.1.17 (Ornithine Decarboxylase); 9002-72-6 (Somatotropin)

Search Phrase:  Ornithine .and. Pituitary

HealthGate Document

Record 1 from database: MEDLINE
Order full text for this document

Title

Sp1 affinity for GC-rich elements correlates with ornithine decarboxylase promoter activity.

Author

al Asadi R; Yi EC; Merchant JL

Address

Division of Gastroenterology, University of Michigan, Ann Arbor, USA.

Source

Biochem Biophys Res Commun, 1995 Sep, 214:2, 324-30

Abstract

The highly conserved ornithine decarboxylase (E.C.4.1.1.17) promoter contains multiple binding sites for Sp1 within the first 400 bp of the cap site. Therefore the ability of individual Sp1 elements to confer transactivation alone or in combination was tested. We show that different Sp1 sites vary in their affinity for Sp1 and that increasing affinity correlates with enhancer activity. In addition, several adjacent Sp1 sites synergistically enhanced promoter activity. Thus, the strength of promoter transactivation correlated with both the number of GC-rich elements and their affinity for Sp1 protein.

Language of Publication

English

Unique Identifier

95408254

Order full text for this document

MeSH Heading (Major)

Ornithine Decarboxylase|BI/*GE; Promoter Regions (Genetics)|*; Transcription Factor, Sp1|*ME

MeSH Heading

Adenoma; Animal; Base Sequence; Binding Sites; Cell Line; Cell Nucleus|ME; Cytosine; Guanine; Human; Molecular Sequence Data; Mutagenesis, Insertional; Oligodeoxyribonucleotides; Oligonucleotide Probes; Pituitary Neoplasms; Rats; Recombinant Proteins|ME; Support, Non-U.S. Gov't; Transfection; Tumor Cells, Cultured

Publication Type

JOURNAL ARTICLE

ISSN

0006-291X

Country of Publication

UNITED STATES

Record 2 from database: MEDLINE
Order full text for this document

Title

Intrinsic and extrinsic factors in estrogen action in human breast cancer: role of polyamines and pituitary factors.

Author

Shiu RP; Lima G; Leung CK; Dembinski TC

Address

 

Source

J Steroid Biochem, 1986 Jan, 24:1, 133-8

Abstract

Although polyamines are important in regulating proliferation of mammalian cells, their role in hormone induction of cell growth has not been delineated. In the estradiol-responsive human breast cancer cell line, T-47D clone 11, estradiol (10(-10) M) was able to stimulate cell proliferation and the activity of ornithine decarboxylase (ODC), the first and rate-limiting enzyme in the biosynthesis of polyamines. alpha-Difluoromethylornithine (DFMO), a specific inhibitor of ODC, blocked the estradiol-induced cell proliferation and ODC activity. Exogenous addition of putrescine, the natural product of ODC, rescued the inhibitory effect of DFMO. In addition, DFMO abolished the estradiol-induced growth of several other estrogen-responsive human breast cancer cell lines but did not affect the growth of hormone-independent cell lines. Further, a serum factor was found to be required for estradiol to exert its effect. To gain insight into the nature of this and possibly other extrinsic factors involved, the effect of estradiol on the proliferation of T-47D cells transplanted into athymic nude mouse was evaluated. In this in vivo system, estradiol alone produced only moderate growth of the human breast tumor. The simultaneous transplantation of a prolactin (PRL)- and growth hormone (GH)-secreting rat pituitary tumor or normal rat pituitary glands at a different site dramatically potentiated the effect of estradiol on the growth of the breast tumor xenograft. Purified PRL or GH were without effect, indicating that the active pituitary factor is neither PRL nor GH. Further, conditioned medium from rat pituitary tumor cells potentiated the mitogenic effect of estradiol on T-47D and several other estrogen receptor-positive human breast cancer cell lines in vitro under serum-free condition. In conclusion, we have identified both intrinsic (polyamines) and extrinsic (pituitary/serum) factors that are importance for estrogen to exert its mitogenic action. The next goal will be to elucidate the mechanisms of action of these molecules in the modulation of estrogen action.

Language of Publication

English

Unique Identifier

86201682

Order full text for this document

MeSH Heading (Major)

Breast Neoplasms|*PA; Estrogens|*PD; Pituitary Gland|*PH; Polyamines|*ME

MeSH Heading

Animal; Cell Line; Drug Synergism; Female; Human; Mice; Mice, Nude; Neoplasm Transplantation; Ornithine|AA/PD; Ornithine Decarboxylase|AN; Pituitary Neoplasms|SE; Support, Non-U.S. Gov't; Transplantation, Heterologous

Publication Type

JOURNAL ARTICLE

ISSN

0022-4731

Country of Publication

ENGLAND

CAS Registry/EC Number

EC 4.1.1.17 (Ornithine Decarboxylase); 0 (Estrogens); 0 (Polyamines); 70052-12-9 (Eflornithine); 7006-33-9 (Ornithine)

Record 3 from database: MEDLINE
Order full text for this document

Title

Synthesis and biological evaluation of superactive agonists of growth hormone-releasing hormone.

Author

Izdebski J; Pinski J; Horvath JE; Halmos G; Groot K; Schally AV

Address

Department of Medicine, Tulane University School of Medicine, New Orleans, LA 70146, USA.

Source

Proc Natl Acad Sci U S A, 1995 May, 92:11, 4872-6

Abstract

Analogs of the 29 amino acid sequence of human growth hormone-releasing hormone (hGH-RH) with agmatine (Agm) in position 29, desaminotyrosine (Dat) in position 1, norleucine (Nle) in position 27, and L-alpha-aminobutyric acid (Abu) in position 15 have been synthesized, and their biological activity was evaluated. Some peptides contained one or two residues of ornithine (Orn) instead of Lys in positions 12 and 21 and additional replacements in positions 8 and 28. All analogs were found to be more potent than hGH-RH-(1-29)-NH2 in the superfused rat pituitary cell system. In tests in vivo in rats after subcutaneous administration, the analogs JI-22, [Dat1, Orn12,21, Abu15, Nle27, Agm29]hGH-RH-(1-29); JI-34, [Dat1, Orn12,21,Abu15,Nle27, Asp28, Agm29]hGH-RH-(1-29); JI-36, [Dat1, Thr8, Orn12,21, Abu15,Nle27,Asp28,Agm29]hGH-RH-(1-29); and JI-38, [Dat1,Gln8, Orn12,21,Abu15,Nle27,Asp28,Agm29]hGH-RH-(1 -29) displayed a potency 44.6,80.9,95.8, and 71.4 times greater, respectively, than that of hGH-RH-(1-29)-NH2 at 15 min and 217.1, 89.7, 87.9, and 116.8 times greater at 30 min. After intravenous administration, JI-22, JI-36, and JI-38 were 3.2-3.8 times more potent than hGH-RH-(1-29)-NH2 at 5 min and 6.1-8.5 times more active at 15 min. All analogs were found to have higher binding affinities for GH-RH receptors on rat pituitary cells than hGH-RH-(1-29)-NH2. Because of high activity and greater stability, these analogs could be considered for therapy of patients with growth hormone deficiency.

Language of Publication

English

Unique Identifier

95281558

Order full text for this document

MeSH Heading (Major)

Oligopeptides|CS/*PD; Pituitary Gland|DE/*SE; Somatotropin|BL/*SE; Somatotropin-Releasing Hormone|*AA/AG/*CS/PD

MeSH Heading

Amino Acid Sequence; Animal; Comparative Study; Human; In Vitro; Male; Molecular Sequence Data; Rats; Rats, Sprague-Dawley; Receptors, Neuropeptide|ME; Receptors, Pituitary Hormone-Regulating Hormone|ME; Structure-Activity Relationship; Support, U.S. Gov't, Non-P.H.S.

Publication Type

JOURNAL ARTICLE

ISSN

0027-8424

Country of Publication

UNITED STATES

Record 4 from database: MEDLINE
Order full text for this document

Title

Ornithine decarboxylase immunoreactivity in the pituitary gland. A comparative lightmicroscopical study.

Author

Müller M; Bernstein HG; Aurin H; Järvinen M; Pajunen AE

Address

Institute of Neurobiology and Brain Research, Magdeburg, Germany.

Source

Cell Mol Biol, 1991, 37:2, 119-24

Abstract

In the present study efforts are made to localize ornithine decarboxylase enzyme protein--the key enzyme of polyamine biosynthesis--in the adenohypophysis of different vertebrates by means of immunocytochemistry. The antigenic expression of ornithine decarboxylase was revealed in the pituitary of the clawed frog (Xenopus laevis D.), but not in rat and human adenohypophysis. The immunocytochemical results are compared with the staining pattern of the periodic acid-Schiff-reaction. No correlation between these results and the immunocytochemically obtained data has been found. Conclusions are drawn from the location of the enzyme and possible phylogenetic and humoral regulation mechanism.

Language of Publication

English

Unique Identifier

91347299

Order full text for this document

MeSH Heading (Major)

Ornithine Decarboxylase|*AN; Pituitary Gland|*EN; Pituitary Gland, Anterior|*EN

MeSH Heading

Animal; Comparative Study; Cytoplasm|EN; Human; Immunoenzyme Techniques; Rats; Rats, Inbred Strains; Xenopus laevis

Publication Type

JOURNAL ARTICLE

ISSN

0145-5680

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 4.1.1.17 (Ornithine Decarboxylase)

Record 5 from database: MEDLINE
Order full text for this document

Title

Pancreatic tumoral cell line AR42J: an amphicrine model.

Author

Christophe J

Address

Department of Biochemistry and Nutrition, Medical School, UniversitÆe Libre de Bruxelles, Belgium.

Source

Am J Physiol, 1994 Jun, 266:6 Pt 1, G963-71

Abstract

AR42J cells derive from azaserine-induced malignant nodules from the rat pancreas. They differ from normal acinar cells for at least three reasons: 1) they proliferate rapidly; 2) they synthesize, store, and secrete digestive enzymes but the regulation of their exocrine function is abnormal, from the emergence of atypical receptors (e.g., cholecystokinin octapeptide type B and pituitary adenylate cyclase-activating polypeptide type I receptors) to unusual inositol phosphate metabolism and cytoskeleton disorganization; and 3) they possess an added neuroendocrine-regulated pathway characterized by voltage-sensitive ionic currents, post-translational processing of peptidic prohormones (and possibly autocriny), and the release of small neurotransmitters (gamma-aminobutyric acid, glycine, and glutamic acid). These amphicrine cells represent, therefore, a cancerous version of the primordial pancreatic ductular epithelium. Dexamethasone favors their differentiation toward the exocrine phenotype. The mitogenic pathway is favored by the occupancy of receptor tyrosine kinases, adenosine 3',5'-cyclic monophosphate, ornithine decarboxylase expression, and Na(+)-H+ exchange. Somatostatin opposes proliferation through protein phosphatases.

Language of Publication

English

Unique Identifier

94295709

Order full text for this document

MeSH Heading (Major)

Pancreatic Neoplasms|*SE; Tumor Cells, Cultured|*

MeSH Heading

Animal; Cell Differentiation; Dexamethasone|PD; Digestion; Enzymes|SE; Exocytosis; G-Proteins|PH; Human; Ion Channels|ME; Receptors, Cholecystokinin|ME; Signal Transduction; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0002-9513

Country of Publication

UNITED STATES

Record 6 from database: MEDLINE
Order full text for this document

Title

Mechanism of action and pure antiandrogenic properties of flutamide.

Author

Labrie F

Address

Medical Research Council Group, Le Centre Hospitalier de l'Universite Laval Research Center, Laval University, Québec City, Canada.

Source

Cancer, 1993 Dec 15, 72:12 Suppl, 3816-27

Abstract

Although treatment of intact adult male rats with the pure antiandrogen flutamide or a luteinizing hormone-releasing hormone (LHRH) agonist alone leads to partial inhibition of ventral prostate weight, maximal inhibition is achieved by combination of the two drugs. Potentializing effects of the two compounds were observed even on prostatic ornithine decarboxylase activity. Because LHRH agonists are widely used to achieve medical castration in men treated for prostate cancer, it is of interest to observe that in the dog, known for being the best model for studies of the action of LHRH agonists, flutamide does not interfere with the potent desensitizing action of the LHRH agonist on pituitary LH secretion, thus supporting the combined use of flutamide with an LHRH agonist for maximal androgen blockade without loss of efficiency of the LHRH agonist. Because prostate cancer is known to show a high degree of heterogeneity of its sensitivity to androgens, we analyzed the effect of combined antiandrogen therapy on parameters more sensitive to androgens than ventral prostatic weight itself. In agreement with its pure antiandrogenic characteristics, flutamide alone has no stimulatory effect on the intraprostatic level of mRNA encoding the C1 or C3 component of prostatic binding protein (PBP), whereas cyproterone acetate (CPA), megestrol acetate (MEG), and, especially, medroxyprogesterone acetate (MPA) markedly stimulate PBP-C1 and PBP-C3 mRNA levels, an effect reversed by flutamide, thus further supporting the intrinsic androgenic activity of all these steroidal derivatives. Similar androgenic effects of the steroidal derivatives were observed on prostatic ornithine decarboxylase activity. Androgen-sensitive Shionogi tumor cells were then used to assess the antiandrogenic/androgenic properties of flutamide and the above-indicated steroidal derivatives. MPA, MEG, CPA as well as spironolactone-stimulated cell proliferation under both in vivo and in vitro conditions, thus illustrating the intrinsic androgenic activity of all these compounds. Flutamide was inactive by itself and reversed the stimulatory effect of all other compounds, thus indicating its pure antiandrogenic activity. Although castration reduces intraprostatic dihydrotestosterone (DHT) to undetectable levels in the rat and guinea pig, the concentration remains at about 50% of the value found in intact men after castration, thus indicating an important contribution of the adrenals to DHT in the human prostate, a finding that requires the addition of an antiandrogen to block the action of this important amount of DHT remaining after castration.

Language of Publication

English

Unique Identifier

94073829

Order full text for this document

MeSH Heading (Major)

Androgen Antagonists|*PD; Flutamide|AD/*PD

MeSH Heading

Androgen-Binding Proteins|GE; Animal; Antineoplastic Agents, Combined|PD; Comparative Study; Gonadorelin|AA/AD/PD; Human; LH|BL; Male; Orchiectomy; Ornithine Decarboxylase|ME; Prostate|DE/EN; Prostatic Neoplasms|DT/PA; RNA, Messenger|AN; Stanolone|AN; Tumor Cells, Cultured|DE

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0008-543X

Country of Publication

UNITED STATES

CAS Registry/EC Number

EC 4.1.1.17 (Ornithine Decarboxylase); 0 (prostatic binding protein); 0 (Androgen Antagonists); 0 (Androgen-Binding Proteins); 0 (Antineoplastic Agents, Combined); 0 (LHRH, Trp(6)-des-GlyNH2(10)-); 0 (RNA, Messenger); 13311-84-7 (Flutamide); 33515-09-2 (Gonadorelin); 521-18-6 (Stanolone); 9002-67-9 (LH)

Record 7 from database: MEDLINE
Order full text for this document

Title

Activity of ornithine decarboxylase (ODC) and polyamine levels as biochemical markers of malignancy in human brain tumors.

Author

Ernestus RI; Röhn G; Schröder R; Klug N; Hossmann KA; Paschen W

Address

Max-Planck-Institute for Neurological Research, Department of Experimental Neurology, Cologne, Germany.

Source

Acta Histochem Suppl, 1992, 42:, 159-64

Abstract

The content of the polyamines putrescine, spermidine and spermine, and the activity of their metabolic key enzyme ornithine decarboxylase (ODC) were measured in tissue samples obtained during operation of 45 patients with primary or recurrent gliomas, meningiomas and pituitary adenomas. Biochemical analysis and histopathological classification were carried out in the same tumor samples. In benign tumors ODC activity was less than 10 nmol/g/h, whereas in malignant gliomas values up to 34 nmol/g/h were observed. In rapidly growing tumors pronounced heterogeneity was observed with high values in solid tumor parts and low values in necrotic areas. Thus, high ODC activity represents a reliable biochemical marker of malignancy in brain tumors, but low values do not prove benignity.

Language of Publication

English

Unique Identifier

92262733

Order full text for this document

MeSH Heading (Major)

Biogenic Polyamines|*AN; Brain Neoplasms|*CH/PA; Ornithine Decarboxylase|*AN; Tumor Markers, Biological|*AN

MeSH Heading

Adenoma|CH/PA; Brain|EN/PA; Brain Chemistry|PH; Glioma|CH/PA; Human; Meningeal Neoplasms|CH/PA; Meningioma|CH/PA; Neoplasm Recurrence, Local; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE

ISSN

0567-7556

Country of Publication

GERMANY

CAS Registry/EC Number

EC 4.1.1.17 (Ornithine Decarboxylase); 0 (Biogenic Polyamines); 0 (Tumor Markers, Biological)

Record 8 from database: MEDLINE
Order full text for this document

Title

Short-chain analogs of luteinizing hormone-releasing hormone containing cytotoxic moieties.

Author

Janáky T; Juhász A; Rékási Z; Serfözö P; Pinski J; Bokser L; Srkalovic G; Milovanovic S; Redding TW; Halmos G; et al

Address

Endocrine, Polypeptide and Cancer Institute, Tulane University School of Medicine, New Orleans, LA 70146.

Source

Proc Natl Acad Sci U S A, 1992 Nov 1, 89:21, 10203-7

Abstract

Five hexapeptide and heptapeptide analogs of luteinizing hormone-releasing hormone (LH-RH) were synthesized for use as carriers for cytotoxic compounds. These short analogs were expected to enhance target selectivity of the antineoplastic agents linked to them. Native LH-RH-(3-9) and LH-RH-(4-9) containing D-lysine and D-ornithine at position 6 were amidated with ethylamine and acylated on the N terminus. The receptor-binding affinity of one hexapeptide carrier AJ-41 (Ac-Ser-Tyr-D-Lys-Leu-Arg-Pro-NH-Et) to human breast cancer cell membranes was similar to that of [D-Trp6]LH-RH. Alkylating nitrogen mustards (melphalan, Ac-melphalan), anthraquinone derivatives including anticancer antibiotic doxorubicin, antimetabolite (methotrexate), and cisplatin-like platinum complex were linked to these peptides through their omega-amino group at position 6. The hybrid molecules showed no LH-RH agonistic activity in vitro and in vivo but had nontypical antagonistic effects on pituitary cells in vitro at the doses tested. These analogs showed a wide range of receptor-binding affinities to rat pituitaries and cell membranes of human breast cancer and rat Dunning prostate cancer. Several of these conjugates exerted some cytotoxic effects on MCF-7 breast cancer cell line.

Language of Publication

English

Unique Identifier

93066208

Order full text for this document

MeSH Heading (Major)

Antineoplastic Agents|*PD; Cell Survival|*DE; Gonadorelin|*AA/CS/ME/*PD; Oligopeptides|CS/*PD

MeSH Heading

Amino Acid Sequence; Animal; Anthraquinones|PD; Breast Neoplasms|ME; Cell Membrane|ME; Cisplatin|PD; Comparative Study; Doxorubicin|PD; Female; Human; LH|BL; Male; Melphalan|PD; Methotrexate|PD; Molecular Sequence Data; Orchiectomy; Pituitary Gland|ME; Prostatic Neoplasms|ME; Rats; Receptors, LHRH|ME; Structure-Activity Relationship; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Tumor Cells, Cultured

Publication Type

JOURNAL ARTICLE

ISSN

0027-8424

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Anthraquinones); 0 (Antineoplastic Agents); 0 (Oligopeptides); 0 (Receptors, LHRH); 148-82-3 (Melphalan); 15663-27-1 (Cisplatin); 17241-59-7 (2-(hydroxymethyl)anthraquinone); 23214-92-8 (Doxorubicin); 33515-09-2 (Gonadorelin); 59-05-2 (Methotrexate); 9002-67-9 (LH)

Record 9 from database: MEDLINE
Order full text for this document

Title

Comparison of growth hormone response to growth hormone-releasing factor 1-44 according to the combined study of sleep secretion with the responses to pharmacologic stimuli.

Author

Garnier P; Liapi C; Raynaud F; Evain-Brion D

Address

Fondation de Recherche en Hormonologie, Fresnes, France.

Source

Horm Res, 1987, 28:1, 13-9

Abstract

The growth hormone (GH) response to GH-releasing factor (GRF) was studied in 54 severely growth-retarded patients (-2.1 to -6.5 SD) aged from 5 to 20 years (32 males and 22 females), among whom 34 were prepubertal and 20 at early pubertal stages. The patients were also submitted to a standard evaluation of their GH secretion, consisting of at least two classical pharmacologic stimulation (CPS) tests, such as ornithine, arginine and/or insulin, and one study of the GH sleep secretion (SS). The results of the standard evaluation allowed to distinguish 5 groups: (I) endocrinologically normal (n = 26); (II) completely GH deficient (n = 5); (III) partially GH deficient (n = 8); (IV) dissociated GH secretions with normal SS (n = 9), and (V) dissociated GH secretions with low SS (n = 6). The GH responses to GRF were correlated with both responses to CPS and SS. There was a large overlap of the individual responses to GRF between the 5 groups, but the mean responses in groups II, IV and V were significantly lower than in group I. Furthermore, the mean responses of groups IV and V were in the lower range of the normal. It is concluded that the GRF test may be useful to ascertain the diagnosis of functional or partial GH deficiency when the responses to CPS and SS are dissociated.

Language of Publication

English

Unique Identifier

88197053

Order full text for this document

MeSH Heading (Major)

Growth Disorders|*ME; Sleep|*PH; Somatotropin|DF/*SE; Somatotropin-Releasing Hormone|*DU

MeSH Heading

Adolescence; Adult; Child; Child, Preschool; Comparative Study; Female; Human; Male; Pituitary Function Tests|MT; Pituitary Gland|DE/SE

Publication Type

JOURNAL ARTICLE

ISSN

0301-0163

Country of Publication

SWITZERLAND

CAS Registry/EC Number

9002-72-6 (Somatotropin); 9034-39-3 (Somatotropin-Releasing Hormone)

Return to the HealthGate Home Page.

SUBSCRIBE:  The Wednesday Letter is a free electronic monthly newsletter written and published by Karl Loren.  You can view more than 50 back issues of this publication by clicking here.  The Wednesday Letter subscription list is maintained on a secure server, no name is ever given or sold to anyone, and it is never used except for this Newsletter.  It is automatically published on the Tuesday night just before the first Wednesday of every month.  You can subscribe to this free monthly electronic letter by entering your eMail address and name below.  You will then automatically receive a request for confirmation, sent to whatever address you have entered.  If you do NOT receive this confirmation request, then you will not be subscribed.  There may have been an error with your address and you should resubmit.  The letter is never sent twice to the same address -- so you do not have to worry about a duplicate subscription.  When you receive this confirmation request you must reply to it, or your subscription will not become active.  No one can subscribe your name, and address, without you being notified, and if you get an unwanted notice of subscription you only need to DO NOTHING and the subscription will NOT be active.

REMOVAL:  You can remove yourself from the subscription list in several different ways.  Click here to read about this entire newsletter system.  Every edition of The Wednesday Letter is delivered to your address with YOUR name and address in view on the letter, with a link that allows you to remove THAT name from the subscription list.  If you try to send this removal message from an address different from the one you used to send in your original confirmation, then you will get a warning notice first, sent to the subscription address, asking you to confirm that you want to be removed from the list -- by replying to THAT request for confirmation, you will then be automatically removed.  Thus, no one else can unsubscribe you, from some other computer, without your knowledge.  But, if you send in the unsubscribe notice from the same machine used to receive the Letter, then the removal from the subscription list is automatic.

Personal Message:  When you send a personal message to Karl Loren, you will receive a personal reply as per his instructions.  Karl pledges that every personal message will get a personal answer. When you provide your mail address, we will send you free information including our free catalog and a cassette tape lecture by Karl Loren about heart disease, no charge, by mail, even if outside the US.  You can select particular information you would like to receive, along with the free cassette tape and catalog.

You can reach Vibrant Life in many ways, including by mail to Vibrant Life, 2808 N. Naomi St., Burbank, CA 91504.  Within the US and Canada, use the toll free number:  (800) 523-4521, the local number:  (818) 558-1799, the FAX:  (818) 558-7299, eMail to kimberly@oralchelation.com or any one of the hundreds of message forms throughout the 50 web sites.  Vibrant Life normally ships the same day we get an order.  There are message forms on each of the 100,000+ pages on this and other sites where you can communicate with Vibrant Life.  Check out our companion site, at:  http://www.oralchelation.net where Karl's 2000 page book is published.  Karl Loren is the author and webmaster for this BOOK, as well as for another web site about ORAL CHELATION.  His personal philosophical articles are at PHILOSOPHY. 

Copyright © May 10, 2012 12:06 AM by Karl Loren on behalf of Vibrant Life, ALL RIGHTS RESERVED.  Permission is granted for non-commercial downloading, copying, distribution or redistribution on two conditions:  One, that some form of copyright notice is included in every copy distributed or copied, showing the copyright belonging to Vibrant Life, Burbank, CA, at www.oralchelation.com . The second condition is that the material is not to be used for any purpose contrary to the purposes and objectives of this site.  This permission does not extend to materials on this site which are copyrighted by others.